Biomedical subjects

R Grenman

Publications and source records attributed to R Grenman.

50 records · Page 3Linked to original sources

PubMed1991

Measurement of human cochlear blood flow.

Cochlear blood flow (CBF) was measured with a laser-Doppler (L-D) flowmeter (Periflux PR2-B) in four unanesthetized human subjects with chronic tympanic membrane perforations and nine anesthetized human subjects undergoing middle ear operations. The L-D recordings were made over the promontory and/or the round window membrane during carbogen breathing and direct electrical stimulation of the cochlea in both groups and with warm water irrigation of the external ear canal in the anesthetized subjects. Carbogen led to little or no change in CBF as monitored with either measurement approach in either subject group. Electrical stimulation yielded an increase (15% to 25%) in CBF as recorded from the promontory in seven of the nine subjects tested. Warm (44 degrees C to 49 degrees C) water irrigation produced changes of 20% to 60% in CBF that were partially recoverable in the 10 minutes available for study. This study demonstrated the feasibility of direct CBF measurement in humans with the L-D method. Moreover, the data indicate that carbogen has little influence on CBF and that electrical stimulation at relatively safe levels and warm water irrigation of the ear canal produce increases in human CBF.

Aged↗

PubMed1989

Radiation response of vulvar squamous cell carcinoma (UM-SCV-1A, UM-SCV-1B, UM-SCV-2, and A-431) cells in vitro.

Standard therapy for squamous cell carcinoma (SCC) of the vulva consists of radical surgery and inguinal node dissection. Radiation therapy has been used for preoperative treatment in advanced cases to reduce the size of the tumor, and also as the only treatment in inoperable or recurrent disease. To study the inherent radiation sensitivity of vulvar carcinoma, we tested three new vulvar carcinoma cell lines and the long-established cell line A-431 by using a 96-well plate clonogenic assay, earlier shown by us to be suitable for survival studies of SCC. SCC and adenocarcinoma cell lines derived from other sites were used as a reference. Cells were irradiated with a 4-MeV linear accelerator at a dose rate of 2.0 Gy/min. The vulvar cell lines were found to be highly resistant to radiation with the average mean inactivation dose of 3.44 +/- 0.34 Gy as calculated from the area under the curve. The results were consistent in repeated experiments and for all cell lines. The average value for area under the curve was 1.79 +/- 0.30 for the other SCC lines tested. The values for area under the curve differed significantly (P less than 0.0001) between the vulvar lines and reference SCC lines. These results indicate that vulvar SCC cells in vitro express exceptional inherent radioresistance, and thus development of other forms of additional treatment would be more advantageous in advanced cases.

Carcinoma, Squamous Cell↗

PubMed1989

Clonogenic cell assay for anchorage-dependent squamous carcinoma cell lines using limiting dilution.

Clonogenic assays under either anchorage-dependent or -independent conditions are very useful for testing the sensitivity of tumor cells to cytotoxic drugs and radiation. These assays have not been widely used with squamous-cell carcinomas (SCC) because of poor tumor-cell viability and poor cloning efficiency, especially in semi-solid media. To find a clonogenic assay suitable for use with human squamous cancers we tested SCC lines, derived in our laboratory from patients with head and neck cancer, for the capacity to form colonies in soft agar and in 96-well plates. Of 13 UM-SCC lines tested for colony formation in agarose, only UM-SCC-11A was capable of growth in conventional semi-solid media. One other line, UM-SCC-14C, produced colonies in agarose only in the presence of epidermal growth factor. In contrast, all 17 of the SCC lines tested exhibited colony formation in adherent cell culture using limiting dilution in 96-well plates. The plating efficiencies of the SCC lines in the 96-well plate assay ranged from 0.02 to 0.52 colonies (wells)/cell whereas the PE values in soft agar were lower, ranging from 0.0055 to 0.0086 colonies/cell. The 96-well plate assay is not affected by cell migration, a problem encountered with some cell lines when clonogenic assays are performed in Petri dishes. UM-SCC-11A was tested for radiation sensitivity both in soft agar and in the 96-well plate assay. Comparable results were obtained. In summary, the majority of SCC cell lines did not form viable colonies in soft agar but the 96-well plate assay was applicable to a broad spectrum of anchorage-dependent human SCC cell lines and provides an efficient method for evaluating clonogenic cell survival.

Agar↗

PubMed1988

Radiosensitivity of head and neck cancer cells in vitro. A 96-well plate clonogenic cell assay for squamous cell carcinoma.

Radiation sensitivity was determined for nine University of Michigan squamous cell carcinoma (UM-SCC) cell lines, MCF-7 and HeLa, using a 96-well plate clonogenic assay. Plating efficiencies (PE) of the UM-SCC cell lines were between 0.16 and 0.36. Higher PE values obtained were with MCF-7 (0.4) and HeLa (0.5). The UM-SCC cell lines were used at low passages (passage 13 to passage 20) to minimize artifacts attributable to long-term culture. Cells were irradiated in suspension using a cobalt 60 gamma source at a dose rate of 0.94 Gy/min (94 rad/min). Survival data were fitted well by either a linear quadratic function F = e-(alpha D + beta D2) or by a monoexponential function F = Ae-alpha D. Mean inactivation dose, equivalent to the area under the survival curve (AUC), was used as a measure of radiation sensitivity. The UM-SCC-1, 9, 11A, 11B, MCF-7, and HeLa were the most radiation resistant lines we tested (AUC greater than 2.1), while UM-SCC-14A was the most sensitive (AUC = 1.591). The assay was highly reproducible, and the difference in radiation sensitivity between cell lines were statistically significant.

Carcinoma, Squamous Cell↗

PubMed1988

Otoneurological and ultra low field MRI findings in multiple sclerosis patients.

Otoneurological and ultra low field MRI findings in multiple sclerosis patients: 22 patients suffering from multiple sclerosis (MS) underwent thorough neurological and otological examination, extensive ENG testing and Magnetic Resonance Imaging (MRI) examination of the central nervous system. All patients fulfilled the Schumacher criteria for a diagnosis of definitive MS. 20 of the patients had been included in previous otoneurological studies three to five years ago. The general disability assessed according to Hyllested's scale was: Class 1-7, Class 2-4, Class 3-6, Class 4-3, Class 5-2 patients. Thus 11 patients had none or only slight disability. Nevertheless, all patients showed abnormal findings when classified according to the Kurtzke disability scale, which reflects the involvement of separate neuronal entities. The ENG examination revealed abnormal findings in all patients. The most common abnormalities found were as follows: abnormal pendular test 19, ocular fixation index 18, optokinetic nystagmus 14, saccadic eye movements 14 and spontaneous nystagmus 12. 14 patients had uni- or bilateral abnormally slow adduction movements in the saccadic test consistent with internuclear ophthalmoplegia (INO), which is caused by a lesion of the brain stem. MRI examination of the 21 patients studied revealed abnormal findings consistent with MS in sixteen cases. The lesions were unilateral in 5 and bilateral in 11 patients. The most common location for these abnormal findings consistent with MS plaques were in the white matter around the lateral ventricles. Plaques in the brain stem and/or cerebellum were found in only two cases despite numerous clinical and otoneurological findings that indicated the presence of functional lesions in these areas.

Adult↗

PubMed1987

In vitro effects of tamoxifen on UM-SCC head and neck cancer cell lines: correlation with the estrogen and progesterone receptor content.

Eleven squamous-cell carcinoma (SCC) cell lines derived from patients with head and neck cancer were tested together with the MCF-7 breast carcinoma cell line for in vitro growth inhibition by tamoxifen. MCF-7 is known to contain cytosolic receptors for estrogen (ER), progesterone (PgR), androgen (AR) and glucocorticoid. We have previously reported the ER, PgR and AR contents of these 11 head-and-neck SCC cancer lines. Starting from day 3 or 4 after passage, cultures were fed daily with medium containing 5% dextran-charcoal-treated fetal bovine serum (D5) and 0, 1, 2.5, 5, 7.5 or 10 microM tamoxifen. Eight of the 11 SCC lines and MCF-7 showed more than 60% growth inhibition when fed with 5 microM tamoxifen. Of these 8 SCC cell lines, 3 contained both ER and PgR, 4 contained only PgR, and one contained neither receptor. The 3 cell lines that were not inhibited by tamoxifen failed to express either ER or PgR. The action of tamoxifen on the cell lines was further investigated by examining the reversibility and the rate of recovery from tamoxifen-induced growth inhibition in the presence or absence of estrogen. MCF-7 and two ER- and PgR-positive SCC cell lines, UM-SCC-12 and UM-SCC-9, recovered more rapidly when the tamoxifen was replaced with medium containing 17-beta estradiol (E2) than when it was replaced with D5 medium alone. However, of the other tamoxifen-inhibited cell lines studied, each recovered equally well whether the tamoxifen was replaced with D5 medium or with D5 medium containing E2. Furthermore, some cell lines spontaneously resumed growth within 4 to 5 days in the presence of tamoxifen if no new tamoxifen was added to the culture dish. This ability is specific for some cell lines, and further study is required to determine its significance.

Carcinoma, Squamous Cell↗

PubMed1986

Familial olivopontocerebellar atrophy with macular degeneration: a separate entity among the olivopontocerebellar atrophies.

A family with hereditary, neuropathologically confirmed olivopontocerebellar atrophy (OPCA) associated with macular degeneration is described. The mode of inheritance was autosomal dominant. The first symptom was insidious, progressive visual loss caused by macular degeneration. Another early sign was slow saccades. Some years after the visual symptoms, gradually progressing cerebellar dysfunction and pyramidal signs developed. Computed tomography of the brain indicated cerebellar and pontine atrophy. Finally the patients were blind, due to a severe chorioretinal atrophy, and disabled because af motor dysfunction. The present study, together with a review of other reported families with OPCA associated with macular degeneration, suggests that this disorder is a specific and clinically recognizable subtype of OPCA.

Adult↗

PubMed1985

Midline sinuses of the upper lip. Case report.

Nine midline sinuses of the upper lip in eight patients have been described previously. They have been located from the skin under the columella to the frenulum, and have always been directed towards the frenulum. Three new cases are presented: a sinus reaching from the skin of the philtrum to the frenulum in a child with Pierre Robin syndrome, another one in the frenulum of a patient with two separate midline sinuses of the nose, and a third in the frenulum of a child with a partial median cleft lip. The midline sinus is probably caused by disturbed development of the nasofrontal process. The combination of upper lip sinus and Pierre Robin's syndrome is hardly coincidental and supports the concept that the latter is not caused solely by a foetal malposition.

Adult↗

PubMedDate not supplied

Sublethal damage repair in squamous cell carcinoma cell lines.

Squamous cell carcinoma (SCC) cell lines recently established from head and neck tumors were studied for their capability of repairing sublethal radiation induced damage (SLDR). Total doses of 1.25, 2.50, 5.00, and 7.50 Gy were used either as a single dose or split in two equal fractions with a 24 h interval. Cell survival was determined using a 96-well plate clonogenic assay based on limiting dilution. Survival data was fitted by linear quadratic model, and the area under the survival curve (AUC) was obtained with numerical integration. The amount of SLDR was expressed as AUC-ratio comparing survivals from split dose vs single dose experiments. SLDR capacity was observed to vary markedly between individual cell lines (AUC-ratios 1.0-1.5). The relatively radiation-sensitive cell lines had a tendency toward higher SLDR proficiency (correlation coefficient 0.85). The differences in repair capacity could not be explained by the differences in doubling times of the cell lines. The inverse relationship between SLDR capacity and inherent radiosensitivity could explain the poor radiocurability of the sensitive donor tumors. Two of the most resistant cell lines were found SLDR deficient. This is a novel finding, since SLDR has been previously reported in all studied cells.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Core 2 beta1,6-N-acetylglucosaminyltransferases and alpha1,3-fucosyltransferases regulate the synthesis of O-glycans on selectin ligands on oral cavity carcinoma cells.

Selectin-dependent cell binding has importance in the extravasation of blood-circulating tumor cells and in the generation of metastases. Cell surface glycoproteins decorated with sialylated, fucosylated epitopes, such as sialyl Lewis(x) (sLe(x)), are ligands for selectins. Not only terminal sLe(x) moieties but also proximal core structures contribute to the formation of binding epitopes for selectins. Core 2 beta1,6-N-acetylglucosaminyltransferases (C2GnT) and alpha1,3-fucosyltransferases (alpha1,3-FucT) have been suggested to be the rate-limiting enzymes in the synthesis of selectin ligands. We analyzed oral cavity epithelial carcinoma cell lines and showed their expression of RNA transcripts for C2GnT and alpha1,3-FucT, identified alpha1,3-FucT enzyme activities, and analyzed the cell surface sLe(x) expression levels. Neither the pattern of expressed enzymes nor the alpha1,3-FucT activity directly predicted the binding capacity of E-selectin. However, only the sLe(x)-expressing cell lines were capable of binding to E-selectin, but not to P-selectin, thus putatively promoting the selectin-mediated metastasis. These findings suggest that C2GnT in combination with alpha1,3-Fuc-T contribute to the selectin-mediated metastasis in oral cavity carcinomas.

E-Selectin↗

PubMedDate not supplied

Laser bronchoscopy in palliative treatment of malignant obstructing endobronchial tumors.

This retrospective study investigates the experience of our ENT Department in the palliative treatment of obstructive malignant bronchial tumors with endoscopic laser surgery. 82 laser procedures on 39 patients were performed between January 1988 and December 1993. In 25 cases, a carbon dioxide (CO2) laser and, in 14 cases, a combined CO2-Nd:YAG laser were used. In 60 procedures, more than half of the tumor could be resected with laser. In 22 cases, minor improvement of the bronchial airway was achieved. Subjectively, most of the patients felt improved breathing after surgery and all were ready to undergo repeated treatment if it was offered. Two fatal complications occurred. We conclude that endoscopic laser surgery is a relatively safe treatment modality for palliation of a compromised airway and can offer a better life quality to selected patients, although it also involves the possibility of fatal complications.

Adult↗

PubMedDate not supplied

Saccular laryngeal cysts. Three case studies and review of the literature.

Supraglottic laryngeal cysts are benign lesions that usually are easily recognized and simply managed. Among these lesions saccular cysts are uncommon, usually large, anomalies of the larynx and can cause severe airway obstruction and even death. Three patients with a saccular cyst were successfully treated by endoscopic CO(2)-laser excision of their lesions. Before microlaryngoscopy and laser procedure, an urgent tracheostomy was required in 1 of our cases.

Aged↗

PubMedDate not supplied

The effect of irradiation on mitotic and apoptotic frequency in head and neck cancer cell lines, the correlation to p53 mutations and clonogenic survival.

It was our intention to enlighten the controversy between the mainstream of studies and our previous results showing a correlation between the intrinsic radiosensitivity and the p53 allele status of 20 human head and neck squamous cell carcinoma (HNSCC) cell lines. In our study cell lines carrying a wild-type (WT) p53 allele were significantly more radioresistant than cell lines which lacked a WT gene. We observed nine HNSCC cell lines with known intrinsic radiosensitivity and p53 allele status with time-lapse video microscopy after irradiation with 2 and 3 Gy. We studied the mitotic and apoptotic frequencies and scored the apoptoses as to whether they occurred morphologically in mitosis or in interphase. Irradiation with 2 or 3 Gy did not induce apoptosis in the cell lines studied. As expected the mitotic frequency was reduced by the irradiation. This was statistically significant in the cell lines which were radiosensitive when measured with a clonogenic assay. p53 allele status did not have an independent effect on the cell lines, except that the irradiation favoured the apoptosis in mitosis in the cell lines with WT p53 and the apoptosis in the interphase in the cell lines with a mutated or non-functional p53 gene. We conclude that although the apoptosis is not induced by irradiation with 2 Gy or 3 Gy, the p53 suppressor gene seems to influence the process of apoptosis after irradiation in the cell lines studied.

Acridine Orange↗

PubMedDate not supplied

Human papillomavirus and Epstein-Barr virus in epithelial carcinomas of the head and neck region.

BACKGROUND: Human papillomavirus (HPV) DNA has been detected in carcinomas of the upper aerodigestive tract. However, studies of the subject show considerable variation in their results, and the causal relationship between HPV and squamous cell carcinomas of the head and neck area still remains to be determined. Epstein-Barr virus (EBV) is consistently detected in nasopharyngeal carcinoma lesions, but little is known about its association with other carcinomas of the head and neck region. The present study was carried out on the role of HPV and EBV in epithelial carcinomas of the upper aerodigestive tract. MATERIALS AND METHODS: The study material comprised 79 frozen biopsy samples from epithelial head and neck carcinomas. DNA was extracted from frozen biopsy samples for analysis using Southern blot hybridization (SBH) and polymerase chain reaction (PCR) to detect HPV DNA. RESULTS: HPV DNA was detected in 13 samples (16.5%) by SBH under low stringency conditions and in three samples (3.8%) by PCR using general primers targeting the HPV L1 region. HPV seemed to have affinity for labial carcinomas: four of the six samples (66.7%) were HPV DNA positive. The detection rate of HPV diminished from the labial and oral epithelium towards the laryngeal region. In SBH, EBV DNA was not found in any of the biopsy samples. CONCLUSIONS: HPV seems to be involved in multifactorial carcinogenesis in the head and neck epithelium, but the association is not as evident as that found in genital carcinomas. The results suggest that EBV is not associated with sporadic nasopharyngeal carcinomas.

Adult↗