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Biomedical subjects

H Biller

Publications and source records attributed to H Biller.

At least 19 recordsLinked to original sources
PubMed2001

Interferon-gamma secretion of peripheral blood CD8+ T lymphocytes in patients with bronchial asthma: in vitro stimulus determines cytokine production.

It has been postulated that T lymphocytes orchestrate the chronic inflammation in bronchial asthma. In animal models, infiltration of CD8+ T lymphocytes into the bronchial mucosa prevented bronchial hyperresponsiveness and decreased early and late phase reaction. IFN-gamma antagonizes IL-4-dependent IgE production as well as IL-5-induced proliferation and activation of eosinophils. We therefore investigated the secretion of IFN-gamma of isolated CD8+ T lymphocytes from peripheral blood of patients with allergic asthma (n = 6) and from healthy controls (n = 7) in vitro. In this setting we compared the effect of stimulation with anti-CD3 antibodies with that of phorbol myristate acetate (PMA) and calcium-ionophore. As expected, CD8+ T lymphocytes from peripheral blood of healthy volunteers produced significantly more IFN-gamma in the presence of PMA and calcium-ionophore than after stimulation with anti-CD3 antibodies. However, in subjects with allergic asthma, IFN-gamma secretion of CD8+ T cells was significantly higher when incubated with anti-CD3 antibodies than after activation with PMA and calcium-ionophore. While IFN-gamma secretion of CD8+ T lymphocytes of patients with allergic asthma was lower than that of healthy controls in the presence of PMA/calcium-ionophore, it was significantly elevated when compared with normal controls after stimulation with anti-CD3 antibodies. Thus, potent activators of cytokine secretion, such as PMA and calcium-ionophore, induce a cytokine profile different from that induced by weaker stimulants, such as anti-CD3 antibodies. These findings have implications for further studies investigating cytokine production of inflammatory cells in vitro.

Adult↗
PubMed2000

Th1 cytokine pattern in sarcoidosis is expressed by bronchoalveolar CD4+ and CD8+ T cells.

The pathogenesis of pulmonary sarcoidosis has been related to an increased production of Th1-like cytokines. However, cytokine expression in sarcoidosis has not been systematically studied at a single-cell level. We therefore investigated the expression of IL-2, IL-4, IL-13, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) intracellularly in bronchoalveolar lavage (BAL) and peripheral blood CD3+ T lymphocytes from patients with pulmonary sarcoidosis (radiologic stage II-III, n = 8) and normal controls (n = 9) by flow cytometry. In contrast to IL-4 and IL-13, the percentage of T lymphocytes expressing intracellular IL-2 (49.3 +/- 21.3% versus 14.5 +/- 15.6%), IFN-gamma (75.5 +/- 14.9% versus 32.6 +/- 18.7%) and TNF-alpha (68.3 +/- 18.7% versus 36.8 +/- 20.8%) was significantly higher in patients with sarcoidosis than in normal controls (each P < 0.005). In contrast to BAL lymphocytes, expression of these cytokines in peripheral blood lymphocytes did not differ between patients with sarcoidosis and normal controls. Close correlations were observed between the percentages of BAL lymphocytes expressing intracellular IL-2, IFN-gamma and TNF-alpha, but not for IL-4 or IL-13. Analysis of the expression of these cytokines in T lymphocyte subsets revealed IL-2, IFN-gamma, and TNF-alpha in CD4+ as well as CD8+ T lymphocytes, suggesting a contribution of TC1 cells to the production of proinflammatory cytokines in sarcoidosis. We conclude that a Th1-like cytokine pattern can be observed in CD4+ as well as in CD8+ BAL T lymphocytes in patients with pulmonary sarcoidosis.

Adult↗
PubMed1998

Muscle spindles are concentrated in the superior vocalis subcompartment of the human thyroarytenoid muscle.

It is hypothesized that different parts of the thyroarytenoid muscle (TA) are functionally specialized. Specifically, the TA is divided into a lateral muscularis compartment and a medial vocalis compartment. This study examined the distribution of muscle spindles throughout the human TA as an indicator of these functional differences. Histological cross-sections from the anterior, middle, and posterior regions of five human membranous vocal folds were examined for the number and location of muscle spindles. There was an average of 6.1 muscle spindles in sections from each region with no significant variation between the different regions (p < .05). However, in sections from all three regions, the muscle spindles were always found to be concentrated in the superior medial quadrant of the TA (mean 85.9%, p < .01). The inferior medial, superior lateral, and inferior lateral quadrants of the TA contained 11.96%, 2.17%, and 0%, respectively, of the total muscle spindles. Within the superior medial quadrant, most of the muscle spindles were localized in the most superficial part of the muscle. The results of this study demonstrate that the majority of TA muscle spindles are concentrated in its superior medial quadrant, an area we have termed the superior vocalis subcompartment (SC). This finding suggests that the superior vocalis SC is functionally distinct from the remainder of the TA. It is hypothesized that tension in the superior vocalis SC can be controlled independently from the remainder of the TA, and this capability is used to effect the biomechanics of vocal fold vibration during phonation.

Humans↗
PubMed1995

Axons enter the human posterior cricoarytenoid muscle from the superior direction.

OBJECTIVE: To examine the possibility that axons from the superior laryngeal nerve travel inferiorly through connections between the recurrent and the superior laryngeal nerves within the interarytenoid muscle to innervate intrinsic laryngeal muscles. MATERIALS: The branch point from the recurrent laryngeal nerve to the posterior cricoarytenoid muscle was excised from five human larynges. METHODS: The section of nerve was first microdissected to remove the epineurium. Then, the specimen was incubated at 37 degrees C in a 1% collagenase solution, which was alternated with 0.4% chymopapain or 0.25% trypsin. Finally, the specimen was stained with 1% toluidine blue. RESULTS: In all five specimens, axons could be seen entering the nerve branch to the posterior cricoarytenoid muscle from the superior direction. In one specimen, about one third of the axons entering the muscle could be identified as arising from the superior direction. In two cases, the superior axons could be traced back to the recurrent laryngeal nerve branch to the interarytenoid muscle. CONCLUSIONS: These results suggest that axons from the superior laryngeal nerve connect with the recurrent laryngeal nerve in the area of the interarytenoid muscle. Furthermore, these axons travel inferiorly to innervate the posterior cricoarytenoid muscle.

Adult↗
PubMed1994

HPV detection using "hot start" polymerase chain reaction in patients with oral cancer: a clinicopathological study of 64 patients.

We examined the incidence of human papillomavirus (HPV) in intraoral cancers from 64 patients as determined by the highly sensitive technique of "hot start" polymerase chain reaction (PCR) in formalin-fixed paraffin-embedded tissues. Polymerase-chain-reaction-amplified HPV DNA was detected in the carcinomas of 16 patients (25%). The percentage of men in the HPV-positive (HPV+) group was greater than that in the HPV-negative (HPV-) group (86% versus 68%), but the difference was not statistically significant. There was no intraoral site preference for the HPV+ tumors. The mean age of viral-positive and -negative groups was similar (55 versus 53.8 yr). Three of 16 HPV+ patients (19%) had never smoked cigarettes; however, 16% of the HPV- group had also never smoked. Of interest, 38% of patients interviewed had occupation-related exposures that may have contributed to their carcinogenesis, and a disproportionate percentage of these patients (57%) were from the HPV+ group. There were no statistically significant differences between HPV+ and HPV- cases regarding T stage, clinical stage, and tumor differentiation. The disease-free interval did not differ significantly for HPV+ and HPV- patients in total nor when patients were stratified for tumor stage and clinical stage. The only group that showed some difference in outcome was that of the stage III/IV patients with oral cancer. We observed a shorter survival time for the HPV+ patients as compared with the HPV- patients (P = 0.09). We conclude that, in general, HPV is associated with a minority of intraoral cancers and its presence is not predictive of patient outcome.

Adult↗
PubMed1993

Imaging the postoperative neck.

The variety of cervical lymphadenectomy and neck reconstructive procedures that have been developed in the past 20 years has led to confusion about nomenclature in the literature. In addition, some of these operations result in gross alteration of the normal anatomy. The authors review the present classification system for cervical lymph nodes and various lymphadenectomy and reconstructive procedures. Examples of typical postoperative images are given. A protocol for postoperative follow-up is presented, which calls for imaging for 5 years after surgery. Finally, the authors review their experience with 400 cases, 276 of which were initially classified as having no clinical evidence of disease. Recurrence developed in 68 of these (in 62 [91%] within 4-18 months of surgery). Imaging findings altered the postoperative salvage plan in 17 (25%). Clinically occult disease was found at sectional imaging in 47 (17%).

Head and Neck Neoplasms↗
PubMed1993

Analysis of prevalence of human papillomavirus in laryngeal carcinomas. Study of 40 cases using polymerase chain reaction and consensus primers.

In this study we determined the frequency of association of human papillomavirus (HPV) and laryngeal carcinomas and investigated the possibility that HPV may be associated with larger or more aggressive tumors. Laryngeal squamous cell carcinomas from 40 patients who did not have preexisting papillomas by clinical history were retrieved from formalin-fixed, paraffin-embedded blocks and analyzed for HPV. Twenty-two cases were tumors of the true vocal folds, and 18 were supraglottic. Clinical follow-up was available for 25 patients. We used the polymerase chain reaction (PCR) with the "hot start" modification and consensus primers that can detect over 30 distinct HPV types. Three of the 40 patients (8%) had detectable HPV DNA. These 3 patients did not have unusual age demographics and were smokers. All but 1 of the 22 HPV-negative patients who were questioned were also smokers. We compared the outcomes for large (4 cm or greater) HPV-positive and -negative tumors. Six of the 40 tumors were 4 cm or greater and involved contiguous structures. Two of these 6 were HPV-positive, and these patients died of disease after 3 and 16 months, respectively. Of the 4 HPV-negative patients with tumors greater than 4 cm, 3 are disease-free at 41, 42, and 3 months, respectively, and 1 was lost to follow-up. The third HPV-positive patient had a tumor less than 1 cm, and is disease-free after 38 months. While the number of HPV-positive cases is too small for definitive conclusions, it is possible that for large tumors the presence of HPV DNA may portend a worse prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effects of mitomycin-C and etoposide in cell culture and in nude mice: the role of G-CSF mutein.

The combination of mitomycin-C and etoposide showed synergistic cell kill effects in vitro against HEp-2 laryngeal squamous carcinoma cells both in monolayer and in multicellular tumor spheroid systems. This combination was also synergistic in inhibiting HEp-2 tumors growing in nude mice. One course of this combination produced no complete regression of this tumor. When these two agents were combined with recombinant human granulocyte colony-stimulating factor (G-CSF) mutein, the doses of the drugs could be escalated approximately 1.5-fold higher than the doses that were tolerated without G-CSF support. With this modest dose intensification, apparent cure was observed. High-dose mitomycin-C plus etoposide with G-CSF support may be useful for the treatment of patients with inoperable squamous cell carcinoma of the head and neck.

Animals↗
PubMed1992

The intramuscular nerve supply of the posterior cricoarytenoid muscle of the dog.

The paired posterior cricoarytenoid (PCA) muscle has three separate muscle bellies that differ in muscle fiber type (percentage of fast vs. slow twitch) and electromyelographic activity, and, in addition, produce different movements of the arytenoids when stimulated. An investigation of the innervation of the muscle was undertaken to demonstrate the existence of separate functional units. The intramuscular nerve supply of the PCA from five sacrificed dogs were microdissected. The intramuscular nerves of three additional dogs were removed and stained for acetylcholinesterase, which differentiates axons bound for fast- and slow-twitch muscle, and sensory end organs. Three separate fascicles are described entering the PCA muscle from a single branch of the recurrent laryngeal nerve. The three fascicles differ in axon type composition and in sensory, autonomic, and motor percentages, with the ratio of fast twitch to slow twitch varying from 0.78 to 1.5 to 1.7 (P less than .05). This variation supports separate functional capabilities for the three muscle bellies of the PCA.

Animals↗
PubMed1992

Laryngeal chondrosarcomas: a clinicopathologic study of 11 cases, including two "dedifferentiated" chondrosarcomas.

Laryngeal chondrosarcomas are uncommon, and those that contain a distinct, nonchondroid, high-grade spindle cell sarcoma (the so-called "dedifferentiated" chondrosarcoma or chondrosarcoma with additional malignant mesenchymal component [CAMMC]) are extremely rare. Laryngeal CAMMC merit special attention, as CAMMC in other sites portends a poor prognosis. Eleven patients with laryngeal chondrosarcomas are reported on; 2 of these patients had CAMMC. On follow-up, 3 of the 11 patients had recurrences. The first had recurrence 4 and 11 years after tumor enucleation; that patient died disease free 2 years after salvage total laryngectomy. The second had recurrence 2 years after partial laryngectomy and was lost to follow-up after salvage total laryngectomy. The last patient recurred 13 years after partial laryngectomy and underwent salvage total laryngectomy; that patient was one of the two who developed CAMMC, and he also developed stomal recurrence of the "dedifferentiated" component 3 years after total laryngectomy. The other 8 patients are disease free after partial laryngectomy (6) or total laryngectomy (2) 10 months to 12 years later (mean: 51 months). This includes the 1 other patient with CAMMC, who is disease free 60 months after total laryngectomy. Laryngeal CAMMC has been shown, in at least one of the two patients, to be associated with a poor outcome. Patients with recurrent laryngeal chondrosarcomas do not have a poorer outcome after salvage total laryngectomy. The authors advocate partial laryngectomy if technically feasible.

Adult↗
PubMed1990

Salivary duct carcinoma (cribriform salivary carcinoma of excretory ducts). A clinicopathologic and immunohistochemical study of 12 cases.

Salivary duct carcinoma (cribriform salivary carcinoma of the excretory ducts [CSCED]) is an uncommon malignant tumor which occurs predominantly in men (83% in this series; mean age, 61 years) and most often in the parotid gland (92% in this series). The outcome is unfavorable for most patients; of 11 of 12 patients with follow-up, 45% had local recurrence, 54% had distant metastasis, and 45% were dead of disease within 10 years of diagnosis (mean, 3 years). Metastases to lymph nodes were common (72%). Immunohistochemical studies on paraffin-embedded tissue revealed that most tumors reacted with antibodies known to mark adenocarcinoma: B72.3 (11 of 11) and Lewis Y (ten of ten). High and low molecular weight cytokeratins were present in most tumors (nine of ten and seven of nine cases, respectively), supporting the concept that these adenocarcinomas were of ductal origin. Parotid ducts adjacent to CSCED expressed B72.3 in six of nine cases studied, but parotid ducts from normal tissue (adjacent to benign mixed tumors or enlarged periparotid lymph nodes) rarely expressed this marker (one of 17 cases). The detection of B72.3 diffusely in parotid ducts, especially those with atypia, may imply the presence of malignant tumor nearby, which could be useful in evaluating limited tissue from the parotid. However, further studies are necessary to confirm the significance of this finding.

Carcinoma, Intraductal, Noninfiltrating↗
PubMed1989

Human papillomavirus 6/11 and 16/18 in Schneiderian inverted papillomas. In situ hybridization with human papillomavirus RNA probes.

Schneiderian inverted papillomas may be troublesome lesions for clinicians with propensity for recurrences. Dysplasia is not uncommonly seen, and some of these lesions do progress to develop squamous carcinoma. The authors hybridized in situ seven inverted papillomas with RNA probes to human papillomavirus (HPV) 6, 11, 16, and 18. Four of these contained dysplasia, two were without dysplasia, and one contained invasive squamous cell carcinoma. Five inverted papillomas showed evidence of HPV infection based on hybridization. One with mild to moderate and one with severe dysplasia, and one without dysplasia hybridized with mixed probe HPV 6/11. One with mild dysplasia and one associated with invasive squamous cell carcinoma hybridized with mixed probe HPV 16/18. One inverted papilloma without dysplasia and one with severe dysplasia did not definitively hybridize with either mixed probe. These findings raise interesting questions as to role of HPV 6/11 and 16/18 in the development of inverted papillomas, and probably on the progression to and carcinoma.

Adult↗
PubMed1989

Functional mandibular reconstruction of patients with oral cancer.

For the patient with oral cancer who has undergone quadrant resection, mandibular reconstruction provides normalization of the lower facial contour, regained architectural support, and reestablishment of occlusal relationships. Reconstruction with vascularized bone offers the most rapid rehabilitation. Replacement of dentition provides improved deglutition, mastication, and speech. In eligible patients the use of osteointegrated implants can provide rigid stabilization for dental prostheses. In previous studies these implants were placed in a secondary procedure. In the present study microvascular mandibular reconstruction was combined with primary placement of osteointegrated implants in the treatment of seven patients. Preliminary results indicate that the combination of procedures can provide more rapid and effective rehabilitation for the patient with cancer. Issues for further study are also identified.

Adult↗
PubMed1987

Effects of anticancer agents on the shedding of cells from human multicellular tumor spheroids.

We studied the effects of anticancer agents on the inhibition of cell shedding from the surface of multicellular tumor spheroids (MTS). MTS were produced from 2 human tumor cell lines; one melanoma and the other squamous cell lung cancer, by using liquid overlay culture technique. The cell shedding from the melanoma MTS was approximately 10-fold higher than the squamous cell carcinoma MTS. In the melanoma MTS, all 3 drugs studied - vincristine (VCR), doxorubicin (ADR) and cisplatin (DDP)-inhibited cell shedding and the degree of inhibition of cell shedding was drug concentration related. In the squamous cell carcinoma MTS, VCR was as active in inhibiting cell shedding as in the melanoma MTS, but ADR and DDP were less efficacious. When effects on cell shedding were compared with those on cell lethality, VCR produced inhibition of cell shedding at much lower concentrations than those producing cell kill effects. ADR and DDP produced cell lethality as effective as, or more effective than, inhibition of cell shedding. These data seem to parallel known effects of these agents on cell kill and inhibition of metastases. MTS may serve as an in vitro model for the study of cell shedding and metastasis.

Carcinoma, Squamous Cell↗
PubMed1985

Fulminant disseminated carcinomatosis arising from squamous cell carcinoma of the tongue.

Squamous cell carcinoma of the tongue tends to be an indolent disease. Tumors that present as small, localized lesions of the anterior tongue have a median five-year survival greater than 70 percent whether treated by irradiation or surgery. Distant metastases occur in only 7.5 percent. This report describes a well-differentiated T1N0M0 squamous cell carcinoma of the anterior tongue that progressed from diagnosis to death of the patient in less than nine months. At autopsy, the tumor had disseminated widely, including simultaneous metastases to all layers of the heart. It is concluded that factors other than morphology and anatomic extent at presentation may modify prognosis in squamous cell carcinoma of the tongue.

Carcinoma, Squamous Cell↗