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Biomedical subjects

S Hassid

Publications and source records attributed to S Hassid.

At least 37 records · Page 2Linked to original sources

Glycohistochemical characteristics of nasal polyps from patients with and without cystic fibrosis.

OBJECTIVE: To investigate whether cystic fibrosis (CF)-related nasal polyps exhibit significantly distinct glycohistochemical characteristics when compared with single vs massive nasal polyps obtained from patients without CF. DESIGN: Glycohistochemical characteristics were identified by means of 8 histochemical probes, including 5 plant lectins (peanut, gorse seed, wheat germ, Maackia amurensis, and Sambucus nigra agglutinins), 2 animal lectins (14- and 16-kd galectins), and 1 neoglycoprotein (exposing the Thomsen-Friedenreich antigen). The binding of the 8 glycohistochemical markers was determined by means of computer-assisted microscopy. For each probe, 3 quantitative parameters were computed: the labeling index, which describes the percentage of tissue area specifically stained by a given marker; the mean optical density, which reflects the staining intensity; and the concentrational heterogeneity, which characterizes the level of heterogeneity of the staining intensity. SUBJECTS: A series of 61 nasal mucosa specimens was analyzed, including 6 normal cases, 23 single and 18 massive polyposis cases without CF, and 14 nasal polyps associated with CF. RESULTS: Normal and polyposal nasal mucosa differed in terms of the amounts and linkage types of sialic acids (revealed by the wheat germ, M amurensis, and S nigra agglutinins) rather than the characteristics of galactoside expression (monitored with the peanut agglutinin and 2 animal galectins). In contrast, nasal polyps markedly differed between patients with and without CF with respect to galactoside expression (revealed by the peanut agglutinin and the 14-kd galectin) and the display of binding site(s) for the neoglycoprotein. CONCLUSION: Normal and polyposal nasal mucosa differ essentially in sialic acid presentation, while nasal polyps from patients with CF have a higher level of various lectin-reactive galactoside residues than nasal polyps from those without CF.

Cystic Fibrosis↗

Synergistic combinatorial stroke therapy: A quantal bioassay of a GABA agonist and a glutamate antagonist.

We sought to prolong the window for stroke treatment using synergistic combinatorial therapy. We used the intraluminal filament occlusion model in rats to cause focal cerebral ischemia and a quantal bioassay to measure efficacy. The GABA agonist muscimol and the glutamate antagonist MK-801 were used alone and in combination at various times after ischemia onset. At progressively longer treatment delay intervals (30, 60, 75, 120, 240, and 360 min), higher doses of the single drugs were required to achieve neuroprotection. In contrast, the combination 1.0 mg/kg muscimol plus 0.5 mg/kg MK-801 was effective at all delay intervals studied except the longest (P < 0.05 at each time). After 240 min from ischemia onset, the combination was more effective than either single agent (P < 0.05 for each drug dose), suggesting synergism. The neuroprotective effect could not be demonstrated using morphometry. The treatment effects were probably not due to hypothermia because brain temperatures recorded in awake, unregulated subjects remained normo- or slightly hyperthermic following all treatments. Awake subjects kept on a heating pad exhibited mild brain hyperthermia. The combination caused a drop and MK-801 caused a significant increase in mean arterial blood pressure (main effects F(5,172) = 29, P < 0.0001). The combination of a GABA agonist and glutamate antagonist appears to possess synergistic neuroprotective effects when treatment is delayed up to 240 min following the onset of cerebral ischemia. Temperature regulation causes hyperthermia in awake subjects. The quantal bioassay is one method suitable for studies of synergistic stroke therapy.

Animals↗

Correlation of galectin-3/galectin-3-binding sites with low differentiation status in head and neck squamous cell carcinomas.

The accurate determination of levels of differentiation is of prognostic value in human head and neck squamous cell carcinomas (HNSCCs). Because the deliberate selection of biochemical determinants accompanying certain stages of differentiation can refine the predictive power of histochemical assessments, the application of the quantitative evaluation of staining distribution and intensity by computer-assisted microscopy is one prerequisite to potential improvements. We used 2 innovative approaches with peanut agglutinin based on encouraging results with respect to common lectin-histochemistry. First, we used a custom-made neoglycoprotein to monitor the presence of Thomsen-Friedenreich (T) antigen-binding sites. Second, we measured the presence of 2 galectins immunohistochemically and, at the same time, measured lectin-histochemically the presence of accessible ligands for the endogenous lectins. We also monitored the presence of calcyclin, a protein with relevance to cell cycle progression or exocytosis. With 61 cases of HNSCC as their basis, including 31 oral, 20 laryngeal, and 10 hypopharyngeal lesions, the data show that the main modifications observed in connection with a loss of differentiation are related to a modification in the levels of both galectin-3/galectin-3-binding site and T-antigen/T-antigen-binding site expressions. The data obtained also suggest that galectin-3 could act as an acceptor site for the T antigen. Because the level of differentiation is known to be indicative of the recurrence rate in HNSCCs and our data clearly indicate that galectin-3 and the T antigen (and their respective binding sites) are involved in dedifferentiation processes, further investigation is warranted into the roles of galectins in HNSCC tumor progression and recurrence analysis.

Aged↗

Effect of ganaxolone in a rodent model of cerebral hematoma.

BACKGROUND AND PURPOSE: Therapy with gamma-aminobutyric acid (GABA) agonists appears to improve outcome after experimental hematoma but with unacceptable side effects. We looked to synthetic GABA agonists, or positive GABA modulators, widely developed as anticonvulsants and anxiolytics, to find compounds that may be effective. Ganaxolone is a synthetic neuroactive steroid that positively modulates GABA. We sought to determine whether ganaxolone was beneficial using a model of intracerebral hematoma. METHODS: We stereotaxically injected varying doses of bacterial collagenase into the caudate nucleus of rats to induce blood-brain barrier failure and hematoma formation. Four hours later, we administered intravenously 15 or 30 mg/kg ganaxolone (n=23 each group), 20 mg/kg pregnanolone (n=21), or vehicle (n=30). Forty-eight hours after collagenase injection, we rated each animal using a standard rodent neurological examination. The ratings were compared with the amounts of injected collagenase using the quantal bioassay procedure. Other sets of animals were tested later for visuospatial learning. Brains were then prepared for histomorphometry, and brain volumes were estimated. RESULTS: We found that ganaxolone 30 mg/kg significantly increased the ED(50) in the bioassay, for a potency ratio of 1.8+/-0.41 compared with vehicle (P<0.05). Ganaxolone 15 mg/kg and pregnanolone did not affect neurological outcome. Ganaxolone 30 mg/kg did not clearly improve visuospatial learning several weeks after hemorrhage. Ganaxolone exhibited a weak effect on cerebral volumes 48 hours after stroke, but 3 months after hemorrhage no such effect could be detected. CONCLUSIONS: Ganaxolone improves neurological outcome 48 hours after intracerebral hematoma but not visuospatial learning several weeks after intracerebral hematoma. Histological evidence of damage was reduced at 48 hours but not at 3 months.

Animals↗

Intranasal endoscopic surgery in traumatic optic neuropathy--the Belgian experience.

The management of traumatic optic neuropathy remains controversial. In this report we present the results of 8 patients treated by means of an intranasal endoscopic approach to the optic canal after at least 12 hours of corticosteroid therapy without improvement. Vision improved in four of the eight patients who underwent the surgery. There was no morbidity or mortality. As the results of the endoscopic optic nerve decompression are comparable to those reported using other surgical procedures, we feel that this approach merits consideration by surgeons.

Adult↗

Mucins and secreted factors.

Mucin is a large glycoprotein (M up to 4-6.10(6)) with a high content of serine, threonine, and proline residues and numerous O-linked saccharides, often occurring in clusters on the polypeptide. Nine mucin genes exist in humans that encode an apomucin highly modified by O-glycans in forming epithelial mucins. These are variably expressed by epithelial cells of the gastrointestinal, tracheobronchial and reproductive tracts. They may be found either membrane-associated or secreted. As might be imagined from their ubiquitous and complex nature, the biological roles of glycans are quite varied. Protection against infection is an important biological role. Alterations in their carbohydrate moiety have been reported in airway and salivary mucins secreted by patients suffering of cystic fibrosis (CF). Moreover, changes in expression of glycans are also often reported in the setting of transformation and progression to malignancy. Due to the key roles played by glycans of glycoconjugates in both physiological and pathological events, glycobiology and carbohydrate chemistry have become of increasing importance in modern biotechnology.

Carcinoma↗

The levels of expression of galectin-1, galectin-3, and the Thomsen-Friedenreich antigen and their binding sites decrease as clinical aggressiveness increases in head and neck cancers.

BACKGROUND: The aim of this study was to investigate whether an increase in malignancy level is accompanied by significant modifications of the expression of galectin-1, galectin-3, and Thomsen-Friedenreich antigen (T antigen) as well as the expression of binding sites for these three markers in head and neck squamous cell carcinomas (HNSCCs). METHODS: Immunohistochemical and glycohistochemical staining reactions were carried out with antibodies, labeled lectins, and a custom-made neoglycoprotein on the basis of histologic slides from a retrospective series of 40 normal and 75 HNSCC formalin fixed, paraffin embedded tissues, and were quantitatively described with the aid of computer-assisted microscopy. RESULTS: Whatever the histologic type, the epithelial tissues in HNSCC exhibited very significantly (P < 0.01 to P < 0. 0001) lower amounts of galectin-1, galectin-3, and T antigen and their respective binding sites than their corresponding normal counterparts. The tumors of the larynx differed very significantly (P < 0.0001 to P < 0.000001) from all the other tumor types. A loss of differentiation in the HNSCCs is accompanied first by the loss of expression of galectin-3 and galectin-3-reactive sites and then by that of the T antigen and its binding site(s). The opposite feature was observed when the parameters associated with the TNM classification were taken into account. The negative lymph node HNSCCs could be distinguished (P = 0.02) from the positive lymph node HNSCCs on the basis of a loss of galectin-3 expression. The modifications occurring in the extent of expression of galectin-1 and galectin-1-reactive sites were relatively marginal in comparison with those observed for galectin-3-dependent and T- antigen-dependent staining. CONCLUSIONS: The decrease in the extent of expression of galectin-3 and galectin-3-reactive sites, T antigen and T antigen-binding sites, and, to a lesser extent, galectin-1 and galectin-1-reactive sites correlates significantly with an increasing level of clinically detectable HNSCC aggressiveness.

Adjuvants, Immunologic↗

[How do physicians evaluate their medical school training. Retrospective survey of 4 groups of medical students 8-11 years after graduation].

A survey was conducted among 250 graduates of the Bobigny School of Medicine (University Paris-Nord) who had completed medical school from 1986 to 1989 in order to ascertain their opinion concerning the training received. Ninety former students (36%) responded. The mean age of the sample was 34 years; 46 women and 44 men. Most (88.9%) were practicing medicine, principally as general practitioners (61.8%). 81.6% felt they had been well prepared to practice medicine. The rate of satisfaction was higher in the area of fundamental science than in clinical science. The responders generally felt that teaching and validation methods should emphasize real situations. The main criticism concerning the curriculum was an insufficient degree of professionalism, particularly in fields currently of particular importance: epide miology, health economics, education, prevention, office management. Training was also considered to be insufficient in medical techniques, communication, priority decision making, team work, emergency care, organization of time and handling stress. The responders suggested that the future curriculum should focus more on information search, research methodology and computer science. The results of this survey collaborate findings of recent retrospective long-term analyses conducted in other European countries.

Education, Medical, Continuing↗

Prenatal exposure to cigarette smoking is associated with a decrease in arousal in infants.

OBJECTIVE: Sudden infant death syndrome has been related to both exposure to prenatal cigarette smoke and impaired arousability from sleep. We evaluated whether healthy infants born to mothers who smoked during pregnancy had higher auditory arousal thresholds than those born to mothers who did not smoke and whether the effects of smoking occurred before birth. STUDY DESIGN: Twenty-six newborns were studied with polygraphic recordings for 1 night: 13 were born to mothers who did not smoke, and 13 were born to mothers who smoked (>9 cigarettes per day). Other infants with a median postnatal age of 12 weeks were also studied, 21 born to nonsmoking mothers and 21 born to smoking mothers. White noise of increasing intensity was administered during rapid eye movement sleep to evaluate arousal and awakening thresholds. RESULTS: More intense auditory stimuli were needed to induce arousals in newborns (P =.002) and infants (P =. 044) of smokers than in infants of nonsmokers. Behavioral awakening occurred significantly less frequently in the newborns of smokers (P =.002) than of nonsmokers. CONCLUSIONS: Newborns and infants born to smoking mothers had higher arousal thresholds to auditory challenges than those born to nonsmoking mothers. The impact of exposure to cigarette smoke occurred before birth.

Arousal↗

Determination of the levels of expression of sarcolectin and calcyclin and of the percentages of apoptotic but not proliferating cells to enable distinction between recurrent and nonrecurrent cholesteatomas.

OBJECTIVES: To investigate in a series of cholesteatomas 1. whether subgroups of cholesteatomas with specific proliferative/apoptotic features exhibit distinct differentiation markers and 2. whether these different subgroups identified at the biological level relate to specific groups of clinically identified cholesteatomas. STUDY DESIGN: Analysis of 55 cholesteatomas resected by the same surgeon, by means of canal wall up and canal wall down surgical procedures. METHODS: Two differentiation markers were used: biotinylated sarcolectin (to identify sarcolectin-binding sites) and a monoclonal antibody directed against calcyclin (which is the S100A6 protein). The growth pattern in cholesteatomas was characterized at three distinct levels: 1. the cell proliferation level determined by means of the MIB-1 antibody, which enables the Ki-67 cell-cycle-related antigen to be identified on archival material; 2. the apoptosis level determined by means of the in situ labeling of nuclear DNA fragmentation (TUNEL staining); and 3. the p53 tumor suppressor gene-related product determined by means of p53 immunohistochemistry. RESULTS: The cholesteatomas that exhibited the highest proportion of apoptotic cells were those which exhibited the highest level of sarcolectin-binding sites (i.e., sialic acids). In contrast, the cholesteatomas exhibiting the lowest level of both proliferation and apoptosis showed the highest level of calcyclin. Recurrent cholesteatomas can be identified from nonrecurrent ones on the basis of three features, namely, the level of apoptotic cells, the way in which the apoptotic cells are distributed (i.e., homogeneously vs. heterogeneously), and the percentage of calcyclin-positive cells. CONCLUSIONS: The present data emphasize the existence of distinct subgroups of cholesteatomas identifiable at both cell kinetic and differentiation levels. Some of the biological variables used here to identify distinct biological subgroups of cholesteatomas in turn enabled some biological variables to be identified, so making it possible to classify the cholesteatomas in terms of recurrence versus nonrecurrence.

Adolescent↗

Quantitative glycohistochemical characterization of normal nasal mucosa, and of single as opposed to massive nasal polyps.

A series of 41 nasal polyps (23 single and 18 massive) and 6 normal nasal mucosa specimens was glycohistochemically investigated. Five plant lectins were used, i.e., the peanut agglutinin (PNA), the wheat germ agglutinin (WGA), the gorse seed agglutinin (UEA-I), the Maackia amurensis agglutinin (MAA), and the elderberry bark agglutinin (SNA). A neoglycoconjugate and 2 animal lectins (CL-14 and CL-16) were also used. Three quantitative features were calculated by means of computer-assisted microscopy: the percentage of tissue area specifically stained by the histochemical probe, the staining intensity, and the heterogeneity level of the staining distribution. The results show that with respect to sialic acid-glycoprotein binding characteristics as determined by SNA, MAA, and WGA probes, the normal nasal mucosa differed markedly (p<.00001) from the polyposal one. The single nasal polyps exhibited glycohistochemical characteristics that differed markedly (p = .0004) from those exhibited by the massive ones. These differences related mainly to the UEA-I, PNA, and the Thomsen-Friedenreich antigen-exposing neoglycoprotein binding characteristics. In conclusion, the present study shows unambiguously that polyposal mucosa, whether of the single or the massive type, exhibits markedly distinct glycohistochemical characteristics when compared to normal nasal mucosa, and that single nasal polyps also differ markedly from massive ones.

Binding Sites↗

Quantitative glycohistochemistry defines new prognostic markers for cancers of the oral cavity.

BACKGROUND: Histopathologic grading and clinical staging cannot provide a precise prognosis of oral cavity cancer patients. The use of glycohistochemical markers may improve the level of prognostic accuracy of such conventional classification systems. METHODS: Computer-assisted microscopy was employed in a series of 40 oral cavity cancers to determine quantitatively the percentage of positive cells, the staining intensity, and the level of staining heterogeneity for 3 glycohistochemical markers, including peanut agglutinin (PNA), Thomsen-Friedenreich antigen (T antigen) as part of a neoglycoprotein, and sarcolectin. Data were evaluated by discriminant analysis. RESULTS: Although the level of differentiation (P < 0.01 to P < 0.001) and the T variable of the TNM staging system (P < 0.05 to P < 0.01) related mainly to the level of expression of the acceptor sites for PNA and the T antigen, the patient survival period (P < 0.05) was largely a fraction of the level of expression of the acceptor sites for the carrier-immobilized T antigen and for sarcolectin. CONCLUSIONS: In oral cavity cancer, determining the level of acceptor sites for PNA, T antigen, and sarcolectin provides useful information on histopathologic differentiation, clinical staging, and survival. Because these processes of determination were carried out quantitatively, a discriminant model was set up, which enabled the level of oral cavity cancer aggressiveness to be characterized precisely. The current methodology described in this article should therefore afford pathologists original and quantitative (and thus objective) prognostic markers for oral cavity cancers.

Adult↗

Auditory arousal thresholds are higher when infants sleep in the prone position.

OBJECTIVE: To evaluate the possibility that infants sleeping in the prone position have higher arousal thresholds to auditory challenges than when sleeping in the supine position. STUDY DESIGN: Polygraphic recordings were performed for 1 night in 25 healthy infants with a median age of 9 weeks. The infants were exposed to white noises of increasing intensities while sleeping successively in the prone and supine positions, or vice versa. Arousal thresholds were defined by the auditory stimuli needed to induce polygraphic arousals. RESULTS: Three infants were excluded from the study because they awoke while their position was being changed. For the 22 infants included in the analysis, more intense auditory stimuli were needed to arouse the infants in the prone position than those in the supine body position (p = 0.011). Arousal thresholds were higher in the prone than in the supine position in 15 infants; unchanged in 4 infants; and lower in the prone position in 3 infants (p = 0.007). CONCLUSIONS: Infants show higher arousal thresholds to auditory challenges when sleeping in the prone position than when sleeping in the supine position. The finding could be relevant to mechanisms concerned with the reported association between sudden deaths and the prone sleeping position in infants.

Auditory Threshold↗

Sarcoidosis of the paranasal sinuses treated with hydroxychloroquine.

A case of sarcoidosis of the paranasal sinuses is reported. Biopsies of the sinus mucosa showed typical noncaseating granulomas. Hydroxychloroquine, which is known to be active on the cutaneous form of sarcoidosis, was used here with success and is proposed as an effective alternative to high-dose systemic steroids.

Humans↗

Lateral canthotomy: a simple and safe procedure for orbital haemorrhage secondary to endoscopic sinus surgery.

Two cases of orbital complications secondary to functional endoscopic sinus surgery are presented. One case was complicated in the immediate post-operative period with an orbital haematoma, which required urgent decompression using lateral canthotomy. The second case had presented an acute orbital haemorrhage during functional endoscopic sinus surgery, which required the same surgical procedure. These cases demonstrate that lateral canthotomy constitutes a safe and fast surgical procedure to decrease the intraorbital pressure.

Adult↗

Yolk sac tumor of the ear in a child.

OBJECTIVE: This study aimed to describe the clinical, histopathologic, and immunohistochemical findings of the second case of an endodermal sinus tumor of the ear. STUDY DESIGN: This clinical study is a retrospective case report combined with a literature review. SETTING: The patient was treated at the University Erasmus Hospital. INTERVENTION: Diagnosis was confirmed by computed tomographic scan and histologic analysis. The treatment was surgical. RESULTS: The patient underwent surgical treatment, and a locoregional relapse developed. The clinical evolution was in accordance with previous reports of extragonadal endodermal sinus tumor sites. The family refused chemotherapy, and the patient died 3 months after admission. CONCLUSIONS: An endodermal sinus tumor is a malignant germ cell tumor that usually involves the gonadal tissue. Extragonadal sites are rare, and different hypotheses have been evoked to explain these locations. Treatment options include surgical removal and chemotherapy. This is the second case of an endodermal sinus tumor of the ear.

Child, Preschool↗