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Biomedical subjects

M Gunduz

Publications and source records attributed to M Gunduz.

31 records · Page 2Linked to original sources

Middle ear adenoma with neuroendocrine differentiation.

The lining of the middle ear cleft is normally a thin modified respiratory type mucosa. Normal mucosa of the middle ear is devoid of salivary type seromucous glands. Middle ear adenoma is a rare tumor that seems to be derived from the middle ear mucosa. This tumor has been previously described under a variety of names because of its different nature and biological behavior. We herein report a case of middle ear tumor that shows adenomatous and neuroendocrine features. A 64-year-old woman presented with a history of hearing loss, tinnitus and stuffy feeling of the right ear. The patient was treated two times for ear polyp. She finally underwent a tympanomastoidectomy and there was no evidence of recurrence 18 months after the procedure. Histopathological examination displayed cuboidal and columnar cells, arranged as glands, trabeculae and solid sheets. Neuroendocrine differentiation was revealed by immunohistochemical staining with polyclonal antibodies against neuron specific enolase and chromogranin antigens.

Adenoma↗

Squamous cell carcinoma arising in a Warthin's tumor.

Warthin's tumor is a well-defined salivary gland neoplasm consisting of epithelial and lymphoid components. However, malignant transformation is extremely rare. Such a patient who developed squamous cell carcinoma within a Warthin's tumor of the parotid gland is described and possible pathogenesis is discussed.

Adenolymphoma↗

Hearing immaturity found by ABR and its clinical impact on otoneurological evaluation.

Auditory Brainstem Response (ABR) is the most reliable and most frequently used procedure to evaluate audiological conditions in early infancy. However, several reports have demonstrated that developmental change in the central nervous system may affect the results of ABR in audiological evaluations. We examined statistically the reliability of ABR for the diagnosis of profound deafness in early childhood according to our experience over the past 12 years of follow-up in our facility. Subjects included 371 children among 1,041 children who were admitted to Kanariya-Gakuen (institute for pre-school deaf children) from April 1985 to March 1997. These children were examined with ABR to determine their hearing levels. In five cases with an abnormal hearing threshold determined by ABR and other audiological tests, repeated examinations carried out during a 5- to 6-month follow-up period revealed that they had normal hearing. Three of these children had been diagnosed previously with mental retardation and the remaining two were infants < 5 months old. The specificity and sensitivity of ABR were calculated as 97.3% and 100%, respectively. The predictive value of a positive result was 94.7%. There remains the possibility of a false negative for such cases, although the rate seems to be very low (< 0.2%).

Audiometry↗

A gene for fluctuating, progressive autosomal dominant nonsyndromic hearing loss, DFNA16, maps to chromosome 2q23-24.3.

The sixteenth gene to cause autosomal dominant nonsyndromic hearing loss (ADNSHL), DFNA16, maps to chromosome 2q23-24.3 and is tightly linked to markers in the D2S2380-D2S335 interval. DFNA16 is unique in that it results in the only form of ADNSHL in which the phenotype includes rapidly progressing and fluctuating hearing loss that appears to respond to steroid therapy. This observation suggests that it may be possible to stabilize hearing through medical intervention, once the biophysiology of deafness due to DFNA16 is clarified. Especially intriguing is the localization of several voltage-gated sodium-channel genes to the DFNA16 interval. These cationic channels are excellent positional and functional DFNA16 candidate genes.

Adolescent↗

Volume quantification of healthy paranasal cavity by three-dimensional CT imaging.

The volume of the air cavities in the paranasal sinuses is, even at present, not only the simplest but also the most important index employed in the evaluation of the paranasal sinus. We have measured the size of the paranasal cavities in 20 healthy Japanese subjects by reconstructing three-dimensional (3-D) computed tomography (CT) images. To avoid any bias in determining the cavity margin, we first measured bilateral maxillary sinuses of a macaque both by silicone injection and by 3-D reconstruction. Then the CT value for 3-D reconstruction was determined by comparison with the volume measured by direct injection. Each sinus of the healthy volunteers was then measured by 3-D reconstruction imaging. Paranasal sinuses were, individually and on the whole, apparently larger than previously reported: 90.1 ml in males and 72.5 ml in females, on average. Comparing with other body size indices, the increment of the size was quite apparent and the lower prevalence of sinusitis was assumed to play a role in this increased volume of paranasal sinuses in the modern Japanese population.

Adult↗

Human papillomavirus as a risk factor for head and neck cancers--a case-control study.

A retrospective, case-control study was conducted to examine the relationship between the presence of human papillomavirus types 16 and 18 (HPV16/18) DNA and the risk of head and neck cancers. Twelve out of 74 (16.2%) head and neck cancers contained HPV16/18 DNA, while 3 out of 70 (4.2%) non-cancer controls showed HPV16/18 positivity by polymerase chain reaction. The presence of HPV16/18 DNA was associated with an increased risk of head and neck cancer formation, showing an odds ratio of 4.32, with a 95% confidence interval of 1.26-14.78. Although its epidemiological impact might be smaller than that of other factors like cigarette smoking, the presence of HPV16/18 DNA in the aerodigestive tract is suggested to be a risk factor for human head and neck cancers.

Carcinoma, Squamous Cell↗

Dynorphin A1-13 causes elevation of serum levels of prolactin through an opioid receptor mechanism in humans: gender differences and implications for modulation of dopaminergic tone in the treatment of addictions.

Dynorphin peptides act preferentially at kappa- as well as mu- and delta-opioid receptors. This study was conducted to determine whether dynorphin peptides act to lower dopaminergic tone in the tuberoinfundibular system, resulting in elevated serum prolactin levels and, if so, whether such an effect is mediated by the opioid receptors. Dose-related increases in serum prolactin levels were observed after dynorphin A1-13 was administered i.v. in doses of 120 and 500 micrograms/kg to healthy human volunteers with no history of drug or alcohol abuse. Studies were then conducted to determine whether this effect is opioid receptor mediated and, if so, whether at kappa- or mu types. Pretreatment with the opioid antagonist nalmefene (30 mg i.v.), which has high affinity at both mu- and kappa-opioid receptors, caused a greater attenuation in dynorphin A1-13-stimulated increases in serum prolactin levels than pretreatment with similarly high doses of naloxone, an antagonist with lower affinity for both mu- and kappa-opioid receptors. These results suggest dynorphin A1-13 lowers tuberoinfundibular dopaminergic tone through action at kappa- and possibly mu-opioid receptors. Female subjects were significantly more responsive to the prolactin effects of dynorphin than were male subjects. Dynorphin gene expression, dynorphin peptides, and kappa-opioid receptor gene expression and binding have been shown to be altered in response to cocaine administration. Also, both dynorphin peptides and synthetic kappa-opioid agonists have been shown to lower dopamine levels in the nucleus accumbens and to attenuate cocaine-induced surges in dopamine levels. Thus, a dynorphin-like compound capable of reaching critical mesolimbic-mesocortical and nigrostriatal dopaminergic systems may be effective in the management of cocaine addiction.

Adult↗

Nalmefene causes greater hypothalamic-pituitary-adrenal axis activation than naloxone in normal volunteers: implications for the treatment of alcoholism.

Among other actions, opioid antagonists modulate the control endogenous opioids exert on the hypothalamic-pituitary-adrenal (HPA) axis. Naloxone, nalmefene, and naltrexone are the opioid antagonists approved for use in man and are primarily mu-opioid selective. Naltrexone and nalmefene have been demonstrated to be useful in the treatment of alcoholism. Compared with naloxone, nalmefene has a longer half-life, is more potent at the mu-receptor, and has a higher affinity for kappa- and delta-opioid receptors. We conducted an inpatient study comparing the effects of 10 and 30 mg doses of intravenous naloxone and nalmefene in normal, nonsubstance nor alcohol-abusing, volunteers. Significant increases in ACTH and cortisol were observed after both antagonists, without an apparent dose-response relationship; however, both doses of nalmefene resulted in greater HPA axis activation than either dose of naloxone (ACTH: p <0.005). These results indicate that kappa- and delta-opioids may play important roles in the regulation of the HPA axis; nalmefene may be useful as both a probe to explore the HPA axis physiology and as a pharmacotherapeutic agent.

Adrenocorticotropic Hormone↗

Basal total opioid peptide release in the striatum of rats with cholestasis from bile duct resection: a study by the use of in vivo microdialysis.

The opiate withdrawal-like reaction experienced by patients with cholestatic liver disease after the ingestion of the opiate antagonist nalmefene led to the hypothesis that increased opioidergic neurotransmission/neuromodulation in the central nervous system (CNS) contributes to the pathophysiology of cholestasis. The state of antinociception, which is stereospecifically reversed by naloxone, documented in rats with cholestasis from bile duct resection supports this hypothesis. To further study the opioid system in this animal model of cholestasis, we studied the release of endogenous opioid peptides into the extracellular fluid of the dorso-lateral striatum by the technique of in-vivo microdialysis. Total opioid peptide concentration in the dialysate was measured by a solid phase radioimmunoassay with an antibody directed against the N-terminus of the Tyr-Gly-Gly-Phe-X amino acid sequence after acetylation. Basal total opioid peptide release was significantly higher after surgery in both sham resected and bile duct resected animals. However, basal (unstimulated) total opioid peptide release in the striatum of rats was not altered by cholestasis. It is inferred that the opioidergic abnormalities of cholestasis are not associated with an appreciable increase in the release of endogenous opioids into the extracellular fluid of the striatum. Abnormal processing of specific opioid peptides in cholestasis however, cannot be excluded.

Acetylation↗

nm23 Protein expression in larynx cancer and the relationship with metastasis.

The nm23 gene, which encodes nucleoside diphosphate (NDP) kinase, is proposed as a metastatic suppressor gene and has been demonstrated to correlate inversely with metastatic potential in several tumours. To elucidate the role of nm23 in larynx carcinomas, we examined using immunohistochemistry the expression of the nm23 protein in matched sets of primary tumours and metastatic lymph nodes. nm23 Protein was expressed in all the carcinomas as well as in non-neoplastic larynx mucosa. Overexpression of nm23 protein was found in the majority of primary tumours compared with corresponding normal mucosa, while decreased expression was associated with poor differentiation and distant metastasis and/or recurrence. No significant difference in age, sex and stage was found between primary tumours with high and low nm23 protein expression. These results suggest that decreased nm23 protein expression may play a role in metastasis and/or recurrence in larynx cancer and therefore could be used as a prognostic factor.

Adult↗

Naltrexone biotransformation and incidence of subjective side effects: a preliminary study.

When administered orally, naltrexone undergoes extensive biotransformation and is metabolized to 6 beta-naltrexol and other minor metabolites. Naltrexone has been recently approved by the Food and Drug Administration for the treatment of alcohol dependence. An important clinical issue with naltrexone treatment is predicting patient compliance, which may be influenced by adverse side effects experienced during the medication. We investigated whether subjective side effects were related to urinary concentrations of naltrexone and its metabolite 6 beta-naltrexol 3 hr after administration of 50 mg po naltrexone in 24 male moderate-to-heavy social drinkers. The results showed significantly higher levels of urinary 6 beta-naltrexol (p < 0.05) in those subjects who experienced one or more side effect (i.e., headache, nausea, anxiety, or erection). Urinary naltrexone levels did not differ between the groups. Results also showed an approximate 10:1 ratio of 6 beta-naltrexol to naltrexone levels and a significant positive correlation between the parent compound and metabolite, suggesting parallel renal clearance. The results of this study suggest a possible mechanism for the side effects observed after acute administration of naltrexone.

Administration, Oral↗

Characteristics of bone morphogenetic protein-induced chondroid bone: histochemical, immunohistochemical and in situ hybridization examinations.

The third ossification mode, known as transchondroid bone formation, is displayed chiefly in the bone morphogenetic protein (BMP)-induced heterotopic bone formation model. This paper describes the results of histopathological, histochemical, immunohistochemical, and in situ hybridization examinations of BMP-induced heterotopic bone in mice. The research focuses on the localization of typical matrix proteins (peptide and its mRNA) of cartilage and bone--type-I and type-II collagen, osteocalcin and osteopontin--in the chondroid bone matrix.

Animals↗

Apoptosis in normal tissues induced by anti-cancer drugs.

To investigate the damage mediated by anti-cancer drugs in normal cells, we examined the effect of such drugs on apoptosis of normal cells of the small intestinal epithelium and the bone marrow by in situ DNA end-labelling and transmission electron microscopy. Mice received a single dose of 5-fluorouracil (5-FU) or cisplatin, or repeated daily doses of 5-FU for 7 days. In mice treated with a single dose of 5-FU 50 mg/kg or cisplatin 5 mg/kg, the number of apoptotic cells appearing in the small intestine 12 h after injection was relatively small, but increased steadily reaching a peak after 36 h and then decreasing to close to that in the control group by 48 h. In bone marrow cells, results were similar in mice treated with single doses of 5-FU 50 mg/kg but apoptosis increased much less in those treated with cisplatin 5 mg/kg. The proportion of apoptotic cells reached peak values earlier at higher concentrations of 5-FU or cisplatin both in small intestine and in bone marrow. In the mice treated repeatedly with 5-FU 50 mg/kg, the proportion of apoptotic small intestinal epithelial cells reached a succession of peaks at 48-h intervals. Mice treated repeatedly with 5-FU 50 mg/kg also showed a rapid increase in diarrhoea symptoms and a steady decrease in the height of villi. Our results suggest it may be possible to prevent the side-effects of anti-cancer drugs by inhibiting apoptosis in the gastrointestinal tract.

Animals↗