Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural crest cells

Using monoclonal antibodies, we have examined the expression pattern of MASH1, a basic helix-loop-helix protein that is a mammalian homolog of the Drosophila achaete-scute proteins. In Drosophila, achaete-scute genes are required for the determination of a subset of neurons. In the rat embryo, MASH1 expression is confined to subpopulations of neural precursor cells. The induction of MASH1 precedes, but is extinguished upon, overt neuronal differentiation. MASH1 is expressed in the forebrain by spatially restricted domains of neuroepithelium and in the peripheral nervous system exclusively by precursors of sympathetic and enteric neurons. The features of early and transient expression, in spatially restricted subpopulations of neural precursors, are similar to those observed for achaete-scute. Thus, the amino acid sequence conservation between MASH1 and achaete-scute is reflected in a parallel conservation of cell type specificity of expression, similar to the case of mammalian MyoD and Drosophila nautilus. These data support the idea that helix-loop-helix proteins may represent an evolutionarily conserved family of cell-type determination genes, of which MASH1 is the first neural-specific member identified in vertebrates.     

A role for mucosal immunity in resistance to HIV infection

In a recent, thought-provoking novel by Elizabeth McCracken (The Giant's House. Avon Books, New York, 1997), two characters discuss love and its impossibilities. One brashly claims to be "immune to love", explaining the concept to his perplexed interlocutor, "...people become immune to love like they become immune to any disease. Either they had it bad early in life, like chicken pox and that's that; or they keep getting exposed to it in little doses and build up an immunity; or somehow they just don't catch it, something in'em is born resistant. I'm the last type. I'm immune to love and poison ivy". (p. 275) (E. McCracken, The Giant's House. Avon Books, New York, 1997). Substitute the words 'HIV infection' for 'love' and this intriguing metaphor summarizes the state of the art working hypotheses for the phenomenon of resistance to HIV infection in HIV-exposed individuals who, against all odds, do not seroconvert. These hypotheses will be discussed hereafter and particular emphasis will be placed upon a possible role for mucosal immunity in this phenomenon.     

The influence of abductor lever-arm changes after shoulder arthroplasty

Clinically, pain relief is usually satisfactory after shoulder arthroplasty, but the range of motion can be limited. The changes of the lever-arms of deltoid and supraspinatus muscles are considered to be important factors influencing postoperative active motion. After excluding patients with muscle weakness resulting from a neurologic condition, patients with chronic rotator-cuff tears, patients who did not follow rehabilitation guidelines, and patients with bilateral arthroplasties, 22 arthroplasty cases remained and were evaluated. Compared with the unaffected side, four radiologic parameters were assessed: (A) offset of humeral head, (B) lateralization of humeral head, (C) acromiohumeral interval, and (D) superoinferior migration of humeral head. The differences were measured and statistically analyzed. In summary: (1) The active and passive range of motion of abduction in scapular plane were 89.5° ± 26.1° and 109.7° ± 25.0°. (2) Parameters A, B, and C statistically changed (p < 0.05). (3) B value of the operated side was reduced below zero in six (27.3%). (4) There was a tendency to create medial shifting and inferior subluxation with the arthroplasty. This had a moderate adverse correlation to the active range of motion (correlation coefficient 0.498). (5) Before normalization for bone size, only C as a single parameter had moderate correlation with motion; after normalization, this decreased. (6) If combined parameters were assessed, A + C had a moderate correlation (correlation coefficient 0.435) with motion. (7) If an accurate anatomic relationship cannot be completely restored, A seemed more significant than any other parameters (p = 0.002); namely, shoulders with a smaller offset had a more limited active range of motion in abduction.     

Hydrophobic Bombyx mori Silk Fibroin: Routes to Functionalization with Alkyl Chains

Bombyx mori silk fibroin (SF) is a very versatile biopolymer due to its biocompatibility and exceptional mechanical properties which make possible its use as a functional material in several applications. SF can be modified with a large variety of chemical approaches which endow the material with tailored chemical–physical properties. Here, a systematic investigation of different routes is reported to graft long alkyl chains on SF based on both liquid- and solid-phase, aiming to modulate its hydrophobic behavior. The liquid phase method involves direct activation of SF tyrosine residues via diazo coupling and cycloaddition reactions, generating hydrophobic materials insoluble in any common solvent. The solid phase approach consists of the chemical modification of drop-casted SF films by esterification of hydroxyl groups of serine, threonine, and tyrosine SF residues with acyl chlorides of fatty acids. For the solid-state functionalization, a new class of hydrophobic pendant groups is synthesized, based on triple esters of gallic acid anhydrides, that are reacted with the biopolymer to further enhance its resulting hydrophobic features.     

Autosomal recessive hypermyelinating neuropathy

We studied three patients from two kinships, affected by early onset hereditary motor and sensory neuropathy with probable autosomal recessive inheritance (HMSN type III). Morphological studies of sural nerve biopsies revealed an abnormal myelin proliferation. Two adult patients with long-term follow up, lost ability to walk at 28 and 22 years and showed severe involvement of the cranial nerves. Our observations suggest that hypermyelination neuropathy with early onset is a progressive disease with poor long-term prognosis. In one kinship the occurrence of the disease in two sibs of both sexes but not in parents, is consistent with an autosomal recessive inheritance. Familial cases of hypermyelination neuropathy have not been described in previous reports. Morphological aspects of this condition are compared with other forms of hypermyelination neuropathy.Supported by Telethon-Italy for the project: Chronic inflammatory polyradiculoneuropathy: electrophysiological and immunopathological studies     

A comparison of laparotomy and laparoscopy in the management of ovarian masses

To compare the results of laparoscopy with laparotomy in the management of ovarian masses not suspected of being malignant, a retrospective review was made of 115 patients with ovarian masses operated on, 50 by laparotomy and 65 by laparoscopy, in the Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Hong Kong, from November 1, 1992, to October 31, 1993. In the laparoscopy group, the average size of the ovarian masses was smaller, and there was a significant reduction in the intraoperative blood loss, postoperative analgesic requirement, morbidity (particularly febrile morbidity and urinary retention), length of hospital stay, and recuperation period. The incidence of rupture of the ovarian mass was not related to the operative approach but to the underlying pathology. Two patients in the laparoscopy group were converted to laparotomy, and 1 in the laparotomy group required a second laparotomy. The operating time was longer in the laparoscopic approach, but this could be reduced with experience and improved technique in specimen removal. Laparoscopy appears to be a better approach than laparotomy in the management of ovarian masses where malignancy is not suspected and a competent surgeon is available.     

Neuroblastoma in two siblings supports the role of 1p36 deletion in tumor development

Familial neuroblastoma occurs rarely. We studied a family with three children; one of them has a disseminated (stage 4) and another has a localized (stage 2) neuroblastoma. We observed subtelomeric locus D1Z2 (1p36) deletion in both tumors by using double-color fluorescence in situ hybridization. The MYNC gene was found in single copy in both tumors. Loss of heterozygosity (LOH) and restriction fragment length polymorphism analyses were performed by using DNA from frozen tumor cells and from microdissected tumor areas excised from paraffin-embedded sections. We detected somatic LOH at locus D1S468 (1p36) in a tumor-cell population with a trisomy 1 of the stage-2 patient. Neuroblastoma cells of the stage-4 patient were diploid and showed allelic loss at the following loci: D1S172, D1S80, D1S94, D1S243, D1S468, D1S214, D1S241, and D1S164. Haplotype study showed that the siblings inherited the same paternal 1p36-->pter chromosome region by homologous recombination and that, in the two tumors, arm 1p of different chromosomes of maternal origin was damaged. Our results suggest that the siblings inherited the predisposition to neuroblastoma associated with paternal 1p36 region and that tumors developed as a consequence of somatic loss of the maternal 1p36 allele.     

A case-controlled MRI/MRA study of neurovascular contact in hemifacial spasm

BACKGROUND: Neurovascular contact (NVC) with the root exit zone (REZ) of the ipsilateral facial nerve is associated with hemifacial spasm (HFS), but unresolved issues remain. OBJECTIVES: To 1) determine the frequency of symptomatic and nonsymptomatic NVC, 2) determine the features of NVC associated with HFS, and 3) correlate severity of HFS to these features. METHODS: Two independent, blinded, prospective assessments of high-resolution MR and MR angiography (MRA) images were performed on Chinese cases (HFS: n = 44; age-matched control subjects: n = 20). RESULTS: Over 88% of 44 symptomatic sides in patients with HFS had NVC of the ipsilateral facial nerve. At least 80% of symptomatic sides involved NVC at the anterior aspect of the REZ [REZ(ant.)]. Although NVC was observed in approximately half of nonsymptomatic sides, at least 70% of them were not at REZ(ant.). NVC at the cisternal and intracanalicular portions of the facial nerve were not associated with HFS. Half of our patients with HFS had bilateral NVC, but none had bilateral symptoms. Most of our MR/MRA images showed that the size and position of the arterial branches of the vertebrobasilar system were markedly asymmetric. Of patients with bilateral NVC, over 83% had asymmetric NVC sites. The anterior inferior cerebellar artery was the most common vessel involved in NVC, but was not significantly associated with HFS. Most of the NVC involved one vessel at one contact point with no indentation. The development of HFS was significantly associated with nerve indentation in NVC. The development and severity of HFS were not associated with multiple contact points in NVC. No significant interobserver variability existed between the blinded assessments. CONCLUSIONS: MRI/MR angiography are accurate, fast, and safe in characterizing neurovascular contact (NVC) at the brainstem. The site of NVC and ipsilateral facial nerve indentation in NVC are significant determinants for the development of hemifacial spasm (HFS). The lack of bilateral NVC at the anterior aspect of the root exit zone of the facial nerve could explain in part the lack of bilateral symptoms. The development and severity of HFS are not associated with a specific blood vessel or multiple contact points in NVC.     

Induction of electrical excitability by NGF requires autocrine action of a CNTF-like factor

The overlapping expression of neurotrophin and neural cytokine receptors indicates that most neuronal populations are responsive to both classes of factors, yet relatively little is known about how these two trophic signaling systems interact to regulate neuronal phenotype. We report here that one hallmark of NGF's effects on target cells, the induction of membrane electrical excitability, requires the intermediary action of a CNTF-like factor. We found that NGF's regulation of voltage-gated potassium channels, unlike its regulation of voltage-gated sodium and calcium channels, involves a CNTF-like autocrine/paracrine loop. We showed that NGF induces secretion of a soluble factor that mimics the action of exogenous CNTF in regulating voltage-gated potassium channels and that NGF's ability to regulate this potassium channel is blocked by three independent reagents that inhibit the signaling of CNTF and/or related factors. The identity of this autocrine factor does not appear to be CNTF itself. Thus, a CNTF-like autocrine/paracrine factor is both necessary and sufficient for the regulation of potassium channels by NGF and is a key determinant of the type of electrical excitability that NGF induces in target cells.