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Biomedical subjects

J Marais

Publications and source records attributed to J Marais.

At least 19 recordsLinked to original sources
PubMed2001

Evidence for a role of the JNK cascade in Smad7-mediated apoptosis.

Smad proteins are central mediators of the transcriptional effects of transforming growth factor beta (TGF-beta) superfamily that regulate a wide variety of biological processes. Smad7, an inhibitory Smad protein that prevents TGF-beta signaling by interacting with the activated type I TGF-beta receptor, was recently shown to induce sensitization of cells to different forms of cell death. Here we examined the effect of Smad7 on the c-Jun N-terminal kinase (JNK) cascade and investigated the role of this cascade in both the inhibitory and apoptotic functions of Smad7. The transient and stable expression of Smad7 caused a strong and sustained activation of JNK. Expression of a dominant-interfering mutant of mitogen-activated protein kinase kinase 4, which completely abolished Smad7-induced activation of JNK, had no effect on Smad7-mediated inhibition of TGF-beta signaling, indicating that the inhibitory function of Smad7 is independent of the JNK cascade. In contrast, expression of the dominant-interfering mutant of mitogen-activated protein kinase kinase 4 impaired the ability of Smad7 to promote cell death. These experiments reveal a novel link between Smad7 and the JNK cascade, which is essential for potentiation of cell death by this inhibitory Smad.

Animals↗
PubMed2001

c-Jun interacts with the corepressor TG-interacting factor (TGIF) to suppress Smad2 transcriptional activity.

The Sma and Mad related (Smad) family proteins are critical mediators of the transforming growth factor-beta (TGF-beta) superfamily signaling. After TGF-beta-mediated phosphorylation and association with Smad4, Smad2 moves to the nucleus and activates expression of specific genes through cooperative interactions with DNA-binding proteins, including members of the winged-helix family of transcription factors, forkhead activin signal transducer (FAST)-1 and FAST2. TGF-beta has also been described to activate other signaling pathways, such as the c-Jun N-terminal Kinase (JNK) pathway. Here, we show that activation of JNK cascade blocked the ability of Smad2 to mediate TGF-beta-dependent activation of the FAST proteins. This inhibitory activity is mediated through the transcriptional factor c-Jun, which enhances the association of Smad2 with the nuclear transcriptional corepressor TG-interacting factor (TGIF), thereby interfering with the assembly of Smad2 and the coactivator p300 in response to TGF-beta signaling. Interestingly, c-Jun directly binds to the nuclear transcriptional corepressor TGIF and is required for TGIF-mediated repression of Smad2 transcriptional activity. These studies thus reveal a mechanism for suppression of Smad2 signaling pathway by JNK cascade through transcriptional repression.

Animals↗
PubMed2001

Does high-frequency pseudo-random rotational chair testing increase the diagnostic yield of the eng caloric test in detecting bilateral vestibular loss in the dizzy patient?

OBJECTIVES: To assess the incremental diagnostic yield of testing vestibulo-ocular (VOR) gain with high-frequency pseudo-random rotational chair (PsRRC) over testing with bithermal electronystagmography caloric tests in the dizzy patient, particularly in detecting bilateral vestibular loss. PATIENTS AND METHODS: One hundred ninety-eight patients presenting with dizziness underwent PsRRC and caloric testing. The VOR gain on PsRRC was measured at 0.32 to 5.0 Hz, with gain categorized as normal or decreased. PsRRC results were compared with caloric responses, also categorized as normal, or into graded categories of unilateral or bilateral vestibular loss. RESULTS: Reduced PsRRC gain was found in 29 (15%) patients, and reduced caloric tests responses in 70 (35%), with 25 (13%) having bilateral loss. Of patients with reduced chair gain, 25 of 29 (86%) demonstrated bilateral caloric loss. PsRRC gain was normal in most patients with unilateral caloric weakness, but was decreased in all patients with bilateral caloric weakness. The probability of a patient with completely normal caloric responses having an abnormal rotation chair in this study group was under 1% (1 of 128). CONCLUSIONS: PsRRC testing does not offer much additional diagnostic benefit when caloric responses are normal. It is useful in specific conditions, such as unilateral caloric loss for which the patient is not compensating, borderline caloric loss when traditional water caloric tests cannot be used, or for monitoring progressive bilateral vestibular loss.

Adult↗
PubMed1999

Olfactory receptors, Golf alpha and adenylyl cyclase mRNA expressions in the rat heart during ontogenic development.

Golf alpha (a G heterotrimeric protein which shares a high homology with Gs alpha) expression was studied in the rat heart before birth and until weaning. Since Golf alpha in the neuro-olfactory epithelium is coupled to olfactory receptors and type III adenylyl cyclase, we looked for the presence of such molecules in the heart. Golf alpha mRNA was detected in the rat heart, highest levels being found in 21-day old fetuses until 3 days post partum. The protein amounts measured by Western blots paralleled the Golf alpha mRNA levels. Immunohistochemical studies revealed the presence of Golf alpha in atrial and ventricular cardiomyocytes. OL1 and latrophilin mRNAs, G protein-coupled olfactory receptors, were expressed at early postnatal stages. Adenylyl cyclase mRNAs for type II, type III, type V and type VI were expressed before birth and until weaning. Elements for an unexpected signaling pathway involving odorant receptors like OL1 and latrophilin, Golf alpha and type III adenylyl cyclase were expressed in rat heart, and appeared developmentally regulated.

Adenylyl Cyclases↗
PubMed1999

The effect of surgery upon the quality of life in snoring patients and their partners: a between-subjects case-controlled trial.

Snoring is a common complaint in the community. Its psychosocial effect upon the relationship between sleeping partners is not known. This study examines prospectively by detailed tailored questionnaires the differences in the physical, psychological and social aspects in 27 snoring patients and their partners presenting to a snoring clinic and compares them with a control group of 24 patients who had undergone successful Laser-Assisted Uvulopalatoplasty (LAUP) and their partners. All areas examined showed improvement in the non-snoring group, particularly for the patient. Improvement was demonstrated in the non-snoring group's quality of marital state (P < 0.01). Quality of life was improved (P < 0.05). Perceived inadequacies in support were significantly higher in the snoring group (P < 0.05). Evidence of psychiatric disorder apparent in the snoring group was not present in the control group (P < 0.01). This is the first study to demonstrate significant improvement in the quality of life in both patients and their partners, after successful surgery for simple snoring.

Case-Control Studies↗
PubMed1999

Effect of laser uvulopalatoplasty on middle ear function.

OBJECTIVES: Palatal musculature is known to be responsible for the active opening of the eustachian (auditory) tube. Because laser-assisted uvulopalatoplasty (LAUP) may involve partial division of these muscles, the effect of this procedure on middle ear pressures (MEPs) and middle ear volumes (MEVs) was investigated. STUDY DESIGN: A controlled interventional trial with one limb receiving treatment and the other none. Preoperative and postoperative measurements were carried out in both groups. METHODS: A control group of 15 normal volunteers and a study group of 22 patients undergoing LAUP all of whom had normal ears and type A tympanograms before the trial were recruited. Repeat tympanometry was carried out after 3 months in both groups. The results of MEP and MEV were recorded for both groups and analyzed by the Mann-Whitney U test. RESULTS: A trend toward reduced MEP and MEV was noted in the LAUP group, but did not achieve statistical significance. A study with more patients may achieve significance. CONCLUSIONS: No significant effects on middle ear pressures or volumes 3 months after LAUP were demonstrated. A much larger study may, however, arrive at a statistically significant result and further work is warranted. Relevant palatal and tubal anatomy is discussed and a brief review of the relevant literature is given.

Acoustic Impedance Tests↗
PubMed1999

Biodistribution and absorbed radiation dose estimates of 99mTc-labeled dimercaptopropionyl human serum albumin.

UNLABELLED: The use of 99mTc-labeled red blood cells (RBC) for the evaluation of left ventricular function using equilibrium-gated blood-pool imaging suffers from several problems and potential risks. In this study, we estimated the absorbed radiation dose of 99mTc-labeled dimercaptopropionyl human serum albumin (DMP-HSA) as a potential alternative to 99mTc-RBC. METHODS: After the administration of 99mTc-DMP-HSA, whole-body imaging was performed up to 48 h after injection in five volunteers. The heart contents, liver and remainder of the body were used as source organs. Multicompartment modeling of the biodistribution was performed and absorbed radiation dose estimates for 99mTc-DMP-HSA were obtained using the Medical Internal Radiation Dose (MIRD) calculation. RESULTS: Residence times of 0.62 and 0.43 h were obtained for the heart contents and liver, respectively. Radiation dose estimates yielded an effective dose of 0.0055 mSv/MBq. CONCLUSION: 99MTC-DMP-HSA yielded absorbed radiation doses comparable with those of 99mTc-RBC. Therefore, the radiation properties of 99mTc-DMP-HSA are such that it can be used for clinical diagnostic studies.

Absorption↗
PubMed1998

Tonsillitis and chronic psoriasis.

Although the relationship between streptococcal tonsillitis and acute guttate psoriasis is well recognized, its relationship to chronic forms of psoriasis is less established. In order to explore this further, the authors questioned 35 patients with severe psoriasis and 35 age-matched eczema controls about their history of significant sore throats (i.e. requiring a GP visit) and any resultant worsening of the skin condition. A third of the psoriasis patients reported recurrent sore throats which worsened their skin condition. This was true of only one (3%) of the 35 eczema controls. The authors discuss these findings in the context of recent laboratory work on the association between streptococcal infection and psoriasis.

Adult↗
PubMed1998

The value of sedation nasendoscopy: a comparison between snoring and non-snoring patients.

Sedation or sleep nasendoscopy is a widely-used investigation in snorers presenting to otolaryngologists in the UK, despite its non-physiological basis. The presence or absence of snoring and its site of generation were compared between a group of 205 snorers and another of 126 non-snorers. Snoring was produced at nasendoscopy in 45.3% of non-snorers but could not be produced in 18.1% of snorers. There was no significant difference in the site of sound production between the two groups and although the noise produced by the non-snoring group was quieter, this difference was not significant.

Adult↗
PubMed1998

Ototoxicity and topical eardrops.

Topical aminoglycoside ear drops are theoretically acknowledged to be potentially ototoxic when administered in the presence of a tympanic membrane perforation. Although the development of clinical ototoxicity appears to be rare, nine well-documented and incontrovertible cases (12 ears in total) of iatrogenic topical vestibulotoxicity are presented, representing the largest series in the English language world literature to date. All patients were treated with the topical gentamicin-containing ear drops Garasone, (betamethasone sodium phosphate and gentamicin sulphate) for prolonged periods. Toxicity was found to be primarily vestibular rather than cochlear. Further review of five previously reported cases in addition to the findings from another four patients identified with topical ototoxicity are described. Although compensation occurred in unilateral cases the disability in bilateral cases was typically severe and often resulted in litigation.

Administration, Topical↗
PubMed1997

Radiation dose estimates of 186Re-hydroxyethylidene diphosphonate for palliation of metastatic osseous lesions: an animal model study.

A common complication in patients with breast or prostate cancer is bone metastases causing pain. New radionuclide therapy methods have recently been proposed for palliation, including 186Re-hydroxyethylidene diphosphonate (186Re-HEDP). This paper reports on the local development of 186Re-HEDP and the biodistribution studied in animals for eventual use in patients. Adult dose was computed assuming a 70 kg standard man. The 186Re was labelled to HEDP using standard techniques. The biodistribution in five Chacma baboons (Papio ursinus) was studied. Doses ranging from 39.4 to 44.9 MBq kg(-1) (mean 43.6 +/- 2.8 MBq kg[-1]) were administered, corresponding to an adult human dose of 2960 MBq (80 mCi). Whole-body images of the animals were obtained with a dual-headed scintillation camera on an hourly basis for 6 h post-injection and then daily for 3 days. The bone, soft tissue, kidneys and urinary bladder were considered source organs and data from these organs were used in a compartmental model to obtain the mean residence times of the radionuclide in the different source organs. Radiation dose estimates for 186Re-HEDP were subsequently obtained with the MIRDOSE 3 program. The estimated absorbed radiation doses to some of the organs (expressed in mGy MBq[-l]) were as follows: bone surface 1.69; kidneys 0.09; liver 0.04; ovaries 0.04; red marrow 0.75; total body 0.12; urinary bladder wall 0.43. 186Re-HEDP yielded an effective dose of 0.17 mSv MBq(-1). The radiation dose delivered to the bone marrow in this study did not cause any detrimental effect to the baboons, indicating that locally produced 186Re-HEDP is suitable for clinical use.

Adult↗
PubMed1996

Evaluation of samarium-153 and holmium-166-EDTMP in the normal baboon model.

Bone-seeking radiopharmaceuticals such as ethylenediaminetetramethylene phosphonate (EDTMP) complexes of samarium-153 and holmium-166 are receiving considerable attention for therapeutic treatment of bone metastases. In this study, using the baboon experimental model, multicompartmental analysis revealed that with regard to pharmacokinetics, biodistribution, and skeletal localisation, 166Ho-EDTMP was significantly inferior to 153Sm-EDTMP and 99mTc-MDP. A more suitable 166Ho-bone-seeking agent should thus be sought for closer similarity to 153Sm-EDTMP to exploit fully the therapeutic potential of its shorter half-life and more energetic beta radiation.

Absorption↗
PubMed1996

Balance after stapedectomy: the measurement of spontaneous sway by posturography.

Sway was measured by static posturography in 25 patients undergoing stapedectomy, 16 first-side and nine second-side operations. Measurements were taken pre-operatively and at 1 week and 6 months after surgery, 25 age-matched controls were also tested. In both the first and second side groups, sway was greater at 1 week after surgery than pre-operatively when relying on vestibular function alone (P = 0.01 first-side, 0.05 second-side, 0.01 both sides taken together). By 6 months, sway measurements were no longer significantly different from pre-op or control values. Thus, it appears that there is a measurable increase in patients' sway following stapedectomy but this is well compensated by visual and proprioceptive information, and resolves fully with time. Patients undergoing a second side stapedectomy do not appear to fare worse than those undergoing first-side surgery.

Humans↗
PubMed1996

Parental knowledge and experiences after surgery for chronic otitis media.

Sixty-four parents completed questionnaires pertaining to their knowledge, attitudes and experiences both before and two months after their children underwent adenoidectomy and grommet insertion. Although a positive image of and high satisfaction with both procedure and inpatient stay were demonstrated, many parents failed to appreciate the existence, nature and frequency of possible complications. Parents should be given quite explicit descriptions of the most common postoperative problems.

Adenoidectomy↗
PubMed1995

An unusual case of laryngeal pseudotumour.

A pseudotumour represents a lesion that masquerades as a malignant neoplasm. We present an unusual case where the appearance of a tumour was the result of chronic inflammation stimulated by the presence of food matter. This inflammatory reaction resulted in upper airway obstruction associated with a mass lesion and vocal fold palsy.

Aged↗
PubMed1995

The value of radiographic assessment for oropharyngeal foreign bodies.

A double-blind, controlled study to assess the accuracy of interpretation of lateral soft tissue radiographs of 60 patients with suspected foreign body impaction in the oro/hypopharynx was carried out by 18 respondents from three different specialities. All the patients had endoscopy carried out and foreign bodies were present in 25. Of these, foreign bodies were diagnosed on the radiograph in only 38.3 per cent. False-positive diagnoses were made in a mean of 26.3 per cent of those patients who did not have a foreign body.

Double-Blind Method↗