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Biomedical subjects

M Mendelsohn

Publications and source records attributed to M Mendelsohn.

At least 37 records · Page 2Linked to original sources

Visualizing an olfactory sensory map.

We have developed a genetic approach to visualize axons from olfactory sensory neurons expressing a given odorant receptor, as they project to the olfactory bulb. Neurons expressing a specific receptor project to only two topographically fixed loci among the 1800 glomeruli in the mouse olfactory bulb. Our data provide direct support for a model in which a topographic map of receptor activation encodes odor quality in the olfactory bulb. Receptor swap experiments suggest that the olfactory receptor plays an instructive role in the guidance process but cannot be the sole determinant in the establishment of this map. This genetic approach may be more broadly applied to visualize the development and plasticity of projections in the mammalian nervous system.

Animals↗

Transgenes encoding both type I and type IV c-abl proteins rescue the lethality of c-abl mutant mice.

Mice carrying homozygous mutations in the c-abl gene (abl-(m1) or abl2) exhibit severe, though variable phenotypes, including a high rate of postnatal mortality, runting, morphological abnormalities, a susceptibility to infections, and selected immune system defects. To further determine the role of the c-Abl protein in vivo, we have generated three lines of mice expressing c-abl transgenes. These minigenes encode the two major forms of the c-abl gene product (c-Abl types I and IV) and a kinase defective type IV c-Abl. The transgenic lines, in Abl-positive genetic backgrounds, were phenotypically almost indistinguishable from their non-transgene littermates and expressed the c-abl transgene in a variety of tissues at levels comparable to that of the endogenous c-abl gene. When the transgenes were introduced into a mutant c-abl strain by mating, the mutant c-abl phenotype was almost completely rescued by either of the c-abl type I or type IV transgenes, but not by the kinase-defective transgene. These findings suggest that either of the two alternatively spliced c-abl gene products can provide the in vivo functions of c-Abl, and that these functions are dependent on kinase activity.

Animals↗

Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation.

Motor neuron differentiation is accompanied by the expression of a LIM homeodomain transcription factor, Islet1 (ISL1). To assess the involvement of ISL1 in the generation of motor neurons, we analyzed cell differentiation in the neural tube of embryos in which ISL1 expression has been eliminated by gene targeting. Motor neurons are not generated without ISL1, although many other aspects of cell differentiation in the neural tube occur normally. A population of interneurons that express Engrailed1 (EN1), however, also fails to differentiate in Isl1 mutant embryos. The differentiation of EN1+ interneurons can be induced in both wild-type and mutant neural tissue by regions of the neural tube that contain motor neurons. These results show that ISL1 is required for the generation of motor neurons and suggest that motor neuron generation is required for the subsequent differentiation of certain interneurons.

Animals↗

Season of birth and schizophrenia: southern hemisphere data.

OBJECTIVE: The association between winter birth and increased incidence of schizophrenia is well documented in the northern hemisphere. The present study examined season of birth and schizophrenia in a southern hemisphere population from a mild temperate climate. METHOD: The seasonal incidence of birth in schizophrenic patients was compared, using Chi-squared tests, to normative population birth rates. RESULTS: A statistically significant seasonal pattern, with a peak in late spring and early summer, was obtained. CONCLUSION: This supports northern hemisphere findings regarding calendar month, but not season, of excess schizophrenic births. This has implications for viral and other aetiological hypotheses dependent on meteorological factors.

Birth Rate↗

Violent political contexts and the emotional concerns of township youth.

This article presents the findings of a series of studies that examine the perceptions of black South African youth about township life and the civil conflict and violence it encompasses. The studies were conducted with comparable samples of 58-82 youth at 3 points in South Africa's history, all characterized by high levels of violence but differing in terms of their political contexts. These contexts were overt State-community conflict, covert opposition and political repression, and intracommunity violence. The data revealed that in all 3 contexts youth reported a high exposure to violence, but only when violence occurred in the context of intracommunity conflict was it subjectively construed to be the most problematic. Reasons for this may include the real increase in more extreme forms of violence, including deaths, that occurs in intracommunity violence and the blurring of the distinction between political and criminal violence in this context.

Adaptation, Psychological↗

Role of gastroesophageal reflux disease in patients with cervical symptoms.

Otolaryngologists commonly see patients with various nonspecific upper aerodigestive or "cervical" symptoms. The relationship between gastroesophageal reflux disease and these symptoms has been studied but remains unclear. We reviewed the records of 216 patients with various cervical symptoms. Each patient underwent a uniform investigation that included barium swallow, esophageal manometry, acid stimulation testing, and esophagoscopy with distal biopsy. Patients were treated with a combination of a histamine H2 blocker or omeprazole and a prokinetic agent. Follow-up was obtained in 194 patients. Overall, evidence of gastroesophageal reflux disease was detected in 73% of patients. Complete resolution or improvement of symptoms was seen in 84% of patients with treatment. We believe gastroesophageal reflux disease is an important factor in the cause of cervical problems.

Adolescent↗

The aesthetic nose: do we agree?

The surgeon and patient use the preoperative consultations to develop an agreement regarding the aesthetic goals of a rhinoplasty. This study was designed to evaluate whether people do agree on what makes a nose attractive. Computerized video-imaging technology was used to create nine case studies. The graphics software permitted precise modification to either tip projection, tip rotation, or size of the dorsal hump. Only one parameter was altered in each case. Two hundred fifty judges were asked to identify the most attractive image in each case study. Significant trends were observed in each case, but every image received the preference of some judges. Most judges preferred midrange values in eight of nine cases, but overrotation of the tip was preferred to tip droop, overremoval of the dorsal hump was preferred to underremoval, and overprojection of the tip was preferred to underprojection. The discrepancy in what constitutes an aesthetic nose reinforces the need for the surgeon to clearly understand the patient's specific requests rather than to aim to produce a "standard nose.".

Humans↗

Sp1 elements protect a CpG island from de novo methylation.

Animal somatic cell DNA is characterized by a bimodal pattern of methylation: tissue-specific genes are methylated in most cell types whereas housekeeping genes have 5' CpG islands which are constitutively unmethylated. Because methyl moieties derived from the gametes are erased in the morula and early blastula, this profile must be re-established in every generation; this is apparently accomplished by a wave of non-CpG island de novo methylation that occurs at implantation. Using transfection into embryonic stem cells and transgenic mice as a model system, we now show that Sp1 elements play a key role in protecting a CpG island in the adenine phosphoribosyltransferase (APRT) gene from de novo methylation. This recognition mechanism represents a critical step in embryogenesis, as it is responsible for setting up the correct genome methylation pattern which, in turn, is involved in regulating basal gene expression in the organism.

Adenine Phosphoribosyltransferase↗

Differential activation of transcription versus recombination of transgenic T cell receptor beta variable region gene segments in B and T lineage cells.

We have tested the ability of the T cell receptor beta (TCR-beta) transcriptional enhancer (E beta) to confer transcriptional activation and tissue-specific V(D)J recombination of TCR-beta V, D, and J segments in a transgenic minilocus recombination substrate. We find that the minimal E beta element, as previously shown for a DNA segment that contained the E mu element, promotes a high level of substrate D to J beta rearrangement in both B and T cells, but only promotes V beta to DJ beta rearrangement in T cells. Thus, both the E mu and E beta elements similarly direct V(D)J recombination of this substrate in vivo, supporting a general role for transcriptional enhancers in the normal regulation of this rearrangement process. Surprisingly, however, we found that both the V beta and DJ beta portion of the constructs were transcribed in an enhancer-dependent fashion (conferred by either E mu or E beta) in both B and T lineage cells, including normal precursor B cells propagated in culture. These findings indicate that, at least in some contexts, transcriptional activation, per se, is not sufficient to confer V(D)J recombinational accessibility to a substrate V gene segment.

Animals↗

Influence of immunoglobulin heavy- and light-chain expression on B-cell differentiation.

To study the influence of immunoglobulin heavy-chain (HC) and light-chain (LC) expression in promoting B-cell differentiation, we have introduced functional immunoglobulin HC and/or LC transgenes into the recombinase activating gene-2-deficient background (RAG-2-/-). RAG-2-/- mice do not undergo endogenous V(D)J rearrangement events and, therefore, are blocked in B- and T-cell development at the early pro-B- and pro-T-cell stages. Introduction of immunoglobulin HC transgenes into the RAG-2-/- background promotes the development of a B-lineage cell population that phenotypically has the characteristics of pre-B cells. We have shown further that this population has altered growth characteristics as measured by interleukin-7 responsiveness in culture. Bone marrow cells from immunoglobulin HC transgenic RAG-2-/- mice have up-regulated expression of germ-line kappa LC gene transcripts and down-regulated expression of lambda 5 surrogate LCs (SLCs). Although mu HC/SLC complexes are detectable intracellularly in HC/RAG-2-/- pre-B-cell populations, HC expression is not readily detectable on the surface of these cells. lambda LC RAG-2-/- mice had a bone marrow B-lineage cell phenotype indistinguishable from that of RAG-2-/- littermates, indicating that LC expression by itself has no influence on pro-B cell differentiation. Strikingly, simultaneous introduction of mu HC and lambda LC transgenes into RAG-2-/- mice led to the generation of a substantial population of "monoclonal" peripheral B-cells that were functional with regard to immunoglobulin secretion, indicating that T cells or diverse immunoglobulin repertoires are not necessary for peripheral B-cell development.

Animals↗

Viral implications in the formation of multicentric inverting papilloma.

There is growing information to support a viral etiology in inverting papilloma formation. Evidence for this hypothesis comes from clinical findings of multicentricity, high recurrence rates, identification of human papilloma virus (HPV), and the presence of viral-like particles within the tumour tissue. Four cases of multicentric inverting papilloma are presented. In one patient, a squamous papilloma (wart) of the nasal vestibule recurred as an inverting papilloma. Another patient also had a cutaneous wart on the right index finger. These cases and others from the literature are discussed with respect to a viral mode of transmission.

Adolescent↗

Facial plastic surgery database.

Every facial plastic surgeon accumulates a vast library of professional slides and photographs that document his work. Manual cataloguing of the clinical and operative documentation is time consuming and provides limited analysis capabilities. The facial plastic surgery database is a state-of-the-art computer programme that allows the surgeon to sort and locate slides and photographs. Designed for the computer novice, it utilises a simple coding system to permit rapid data input. The codes can be tailored to allow for new procedures or alternative practice styles. There are sophisticated searching routines to quickly find slides and photographs based on any combination of patients and operative criteria. The database also includes an online colour atlas and workspace for recording of presentations. There are automated routines to analyse patients' clinical features, operative trends, and surgical results. Ultimately, examination of this data can be used to facilitate peer review, research, and self-education.

Databases, Factual↗

A comparative study of speech after total laryngectomy and total laryngopharyngectomy.

Quality of voice is an important factor in the consideration of treatment for advanced laryngeal cancer. This prospective study compared the speaking proficiency of patients who used the Blom-Singer valve after total laryngectomy and after total laryngopharyngectomy with jejunal graft reconstruction with that of a group of normal subjects. The total laryngectomy group demonstrated excellent communication ability both face-to-face and on the telephone. They exhibited superior scores for objective intelligibility, subjective intelligibility, acceptability, and intonation when compared with the total laryngopharyngectomy group. Both surgical groups produced similar amplitude and frequency parameters during normal conversation but had limited reserve when these functions were stressed. Despite these quantitative variations, patient acceptance was very high in both surgical groups. These results serve as a foundation for the evaluation and improvement of rehabilitation techniques.

Aged↗

A guided approach to surgery for aspiration: two case reports.

Aspiration frequently occurs in patients with a competent glottis. Analysis using a modified barium swallow (MBS) can reveal an extraglottic mechanism of aspiration in these patients. The MBS examination guided the design of two surgical procedures in patients with severe aspiration. The surgery corrected the underlying extraglottic cause of aspiration while preserving glottic function. In one case the epiglottoplasty controlled aspiration due to spillage over the epiglottis into the airway. In the other case translaryngeal resection of the cricoid lamina combined with cricopharyngeal myotomy controlled aspiration of residue in the hypopharynx. After surgery, both patients had their gastrostomy and cuffed tracheostomy tubes removed and were discharged home on a normal oral diet. Detailed analysis of deglutition by a modified barium swallow can provide a scientific basis to guide the surgical management of patients with severe dysphagia.

Aged↗

Speaking proficiency after primary tracheoesophageal puncture.

Nineteen patients who had undergone total laryngectomy with primary tracheoesophageal puncture underwent comprehensive testing of speaking proficiency. All patients learned to use tracheoesophageal speech in the immediate postoperative period. Overall, their speech was judged as highly intelligible in both objective and subjective testing when assessed by a panel of naive judges. Eighty per cent of all patients were easily understood on the telephone by a naive listener. During conversational speech, quantitative parameters such as vocal amplitude and fundamental frequency were similar to normal speakers. However they demonstrated limitations in vocal range and in peak amplitude when singing or shouting. The ability to produce high quality tracheoesophageal speech from the immediate postoperative period improves quality of life and expedites the overall rehabilitation after total laryngectomy.

Aged↗

New concepts in dysphagia management.

This review presents an outline of the new and expanding role of otolaryngologists in the management of swallowing disorders. It emphasizes an holistic approach to swallowing management. Better understanding of swallowing analysis and the unglamorous yet essential role of conservative management will lead to improvements in surgical treatment and overall patient care.

Deglutition↗

RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement.

We have generated mice that carry a germline mutation in which a large portion of the RAG-2 coding region is deleted. Homozygous mutants are viable but fail to produce mature B or T lymphocytes. Very immature lymphoid cells were present in primary lymphoid organs of mutant animals as defined by surface marker analyses and Abelson murine leukemia virus (A-MuLV) transformation assays. However, these cells did not rearrange their immunoglobulin or T cell receptor loci. Lack of V(D)J recombination activity in mutant pre-B cell lines could be restored by introduction of a functional RAG-2 expression vector. Therefore, loss of RAG-2 function in vivo results in total inability to initiate V(D)J rearrangement, leading to a novel severe combined immune deficient (SCID) phenotype. Because the SCID phenotype was the only obvious abnormality detected in RAG-2 mutant mice, RAG-2 function and V(D)J recombinase activity, per se, are not required for development of cells other than lymphocytes.

Animals↗