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In 1926, Roussy and Lévy described a large family whose members manifested an early onset dominantly inherited gait ataxia, pes cavus, and areflexia, which was eventually associated with distal muscle atrophy, postural tremor, and minor sensory loss. Slow nerve conduction and demyelination of nerve fibers with onion bulb formations in nerve biopsy specimens led to the Roussy‐Lévy syndrome (RLS) being considered a variant of demyelinating Charcot‐Marie‐Tooth disease (CMT‐1). In the present article, we report on the long‐term follow‐up, on nerve biopsy findings, and on the underlying molecular genetic defect in members of the original family studied by Roussy and Lévy. All patients were able to walk during their seventh decade of life. Morphologically, a chronic demyelinating neuropathy with the remarkable aspects of a focally hypertrophic myelin sheath and major loss of myelinated fibers was observed in nerve biopsy specimens of 3 members of this family. Molecular genetic testing identified a previously unknown heterozygous missense point mutation which yielded an Asn131Lys substitution in the extracellular domain of the myelin protein zero (P0). These findings show that the Roussy‐Lévy family belongs to the CMT‐1B subtype and has original morphological and genetic features.

Fixation of penicilloyl groups to albumin in penicillin‐treated patients was shown to involve histidine residues 146 and 338.

A method for studying conformational changes induced in the human albumin molecule, either in its purified form or in serum, is described. Plates were coated with albumin or human serum at varying pHs and were reacted with peroxidase-labeled anti-albumin monoclonal antibodies of different specificities. The data showed that albumin molecules were coated in conformations induced as a result of pH changes, allowing us to demonstrate that pH modifications involved the N-terminal portion of the albumin molecule whether in its purified form or in serum. This method should be applicable to the study of conformational modifications in other proteins as well.

1. A fragment designated D was isolated from human serum albumin degraded by CNBr. Its properties show that it is made up of the B and C fragments isolated by McMenamy et al. (1971) (J. Biol. Chem., 246, 4744-4750). 2. Reduction of fragment D gives rise to two chains, one of which consists of the second subfragment of reduced fragment B linked to fragment C by an amino acid different from methionine. It thus demonstrates the existence of albumin molecules from which the second methionine residue located between fragments B and C is missing.

1. ‘Inhibitor fragment’ isolated from human serum albumin degraded by rabbit cathepsin D is composed of one peptide chain with two intrachain disulphide bonds. There are two kinds of inhibitor molecules having different N-terminal amino acids: one is threonine and the other glutamine. 2. Fragment F1, isolated from inhibitor degraded by trypsin, is composed of two chains linked by a disulphide bond. There are three kinds of fragment F1. All have one alpha chain in common, which has an intrachain disulphide bond. They differ by the nature of the chain, which is linked to the alpha chain by a disulphide bond. The epsilon chain is present in trace amounts. The two other chains, beta and gamma, differ by their C-terminal amino acid, which is respectively arginine and lysine. 3. Inhibitor is composed of the last 92 or 89 residues of the human albumin molecule and fragment F1 is composed of two parts of this C-terminal portion of the albumin molecule.

High performance liquid chromatography (HPLC) was used to determine the association rate constants of antigen-antibody reactions at the solid-liquid interface. The adsorption of human serum albumin (HSA) on monoclonal and polyclonal anti-HSA antibodies immobilized on a HPLC silica support was studied by frontal analysis. The theoretical model assumes irreversible adsorption during the time scale of the experiment. The shape of the breakthrough curves reveals the presence of several kinetic adsorption steps: the model fits well the first part of the elution profile. Frontal analysis gives the apparent adsorption rate constant, which includes the mass transfer in the stagnant fluid phase. This effect can be accounted for by carrying out studies as a function of flow rate on columns packed with adsorbents having various densities of immobilized antibody. Within experimental error, the effective rate constant for the irreversible adsorption process is in good agreement with previous experiments performed by saturating the column with repeated pulse injections.

When human albumin was treated with CNBr, a fragment designated D was obtained and attributed to the absence from some of the albumin molecules of methionine at position 123 [Lapresle & Doyen (1975) Biochem. J. 151, 637-643]. The present study shows that methionine-123 is converted into homoserine without cleavage of the subsequent methionine-cystine bond. With bovine alpha-lactalbumin, a further example of non-cleavage of a methionine-cystine bond with conversion of methionine into homoserine is reported.

The antigenic structure of human albumin was investigated in order to establish whether or not there was any similarity between its antigenic sites. Using immunoadsorbent columns prepared with cyanogen bromide fragments of human serum albumin, antibodies directed against different portions of the albumin molecules were isolated. Measurement of the amount of the antibodies isolated and study of their specificity by inhibition techniques show that these subpopulations of antibodies reacted not only with the fragment used for their isolation (homologous) but also with the other fragments (heterologous). Heterologous fragments were inhibiting only at a very high concentration with regard to the homologous ones. These results show that there is a weak cross-reactivity between different portions of the albumin molecule. This reaction is most probably due to the homology existing in the sequence of the human albumin molecule which has arisen by gene duplication. The same type of behavior can be predicted to extent to other molecules which have evolved by similar mechanisms.

An insoluble specific adsorbent for anti-human serum albumin antibodies was prepared by coupling human serum albumin (H.S.A.) to polystyrene by azo bonds. Rabbit anti-H.S.A. immune serum was passed through a column of the adsorbent. It was shown that different volumes of the immune serum were required for the saturation of the different determinant groups of H.S.A. by their corresponding antibodies. The elution of the anti-H.S.A. antibodies adsorbed on the column was achieved by passing successively through the column an acetate buffer pH 3.0 and a solution of 0.1 N HCl in 0.15 M NaCl. The antibodies were eluted in three different fractions, each of which was composed of γ-globulins only. These three fractions contained different proportions of antibodies of different specificities.

THE SIGNIFICANCE of a pathway directly linking the dentate nucleus of the cerebellum and the contralateral inferior olive has been revealed by clinicoanatomical study of the phenomenon of palatal myoclonus.1-8The lesion which has been most constantly demonstrated in cases of palatal myoclonus (as in rhythmic skeletal myoclonus) is a specific hypertrophic (presumably transynaptic) degeneration of the inferior olive. This hypertrophic degeneration, with very few exceptions,8,9 is associated with a primary lesion in the ipsilateral central tegmental tract1,10-12 or the contralateral dentate nucleus.3,13-14In the first attempt to explain these associations, Guillain and Mollaret4 proposed a triangular relationship among the red nucleus and inferior olive on one side and the contralateral dentate nucleus. However, since no lesion of the olivodentate fibers within the inferior cerebellar peduncle has been associated with palatal myoclonus or hypertrophic olivary degeneration, it subsequently became apparent that this side of

Although cathepsin E is present in trace amounts in spleen from several species, it was found in large amounts in rat spleen. This observation can be correlated with the fact that spleen in the rat is an important organ in haemopoeisis.

Two fixation sites for penicilloyl groups on human albumin were demonstrated. Using CNBr cleavage the first site was located between methionine 123 and methionine 297 and the second one between methionine 297 and the C-terminal residue. In both cases, penicilloyl groups were unmasked by pronase degradation or disulfide bond reduction.

In 1926, Roussy and Lévy described a hitherto undescribed entity which they called "dystasie aréflexique héréditaire." Thus far, no patient has come to postmortem examination, and the nosology of this disease has been a matter of controversy. The finding of numerous onion bulbs in the nerve biopsy specimen from one of Roussy and Lévy's original patients demonstrates that this entity is a form of hypertrophic neuritis.

SOME of the enzymes of bovine spleen have been studied in detail and classified as cathepsin A, B and C according to their specificity for certain synthetic peptides1. Examination of the action of rabbit spleen extracts on human serum albumin has shown the existence of a proteolytic activity having an optimal pH at 3.0–3.5 (ref. 2). It was shown that this activity was not due to an enzyme analogous with cathepsin B or C but could have been due to a cathepsin A (ref. 3). Recently we have demonstrated that this activity was due to a single protease which we have purified by chromatography on modified cellulose4.

Topographical vascular disorders involving combinations of cranial nerves are reviewed in this study These are indicated by the correspondence between groupings of clinical manifestations and anatomical vascular distributions Confirmatory evidence is provided by mishaps, following diagnostic or therapeutic angiography. Three systems play a role in the vascularization of cranial nerves. the inferolateral trunk (ILT), most often arising from the internal carotid artery, the middle meningeal system (MMS), and the ascending pharyngeal system (APS), the latter two are both derived from the external carotid artery. Conclusions concerning the ILT are least definite because of variations in vascular territory and the lack of confirmation from embolic events in a vascular region that is rarely the site of embolization. The specific ILT territory includes cranial nerve III and also nerves IV, VI and V1 Knowledge of the vascularization of nerve III may furnish explanations as to its different modes of involvement in diabetes mellitus. For the MMS, the cranial nerves concerned are V2, V3 and VII Two vascular territories for the intrapetrous portion of nerve VII are defined: the first (stylomastoid artery) is limited to nerve VII, the second (MMS) supplies VII and V Two examples of involvement of VII and V following selective MMS embolization are presented. A study of Bells palsy associated with nerve V impairment is summarized. The APS supplies nerves IX, X, XI and XII; XI has a dual vascularization which explains why it can either be spared (as was the case in an angiographic accident) or involved (as in a case of herpes zoster) A vascular mechanism should be considered when cranial nerve lesions occur in the syndromes described here

TO THE EDITOR.— I read with interest the article titled "Sensorimotor Stroke Due to Thalamocapsular Ischemia" published in the December issue of the Archives (34:739-741, 1977). In this article the authors state that their case appears to be unique.In 1960, the now late Garcin and I reported a rather similar case.1 A thalamic lacuna was responsible for a chiro-oral sensory disorder as previously described,2 associated at the beginning with an ipsilateral motor deficit of fingers. Postmortem examination, six years after the onset of the symptoms, failed to disclose any substantial lesion in the internal capsule. However, we postulated that there is a transitory involvement of this structure that is due to the vicinity of the thalamic lesion. The slight demyelination of the internal capsule observed by Mohr and associates, in which case the autopsy was performed three months after the stroke, would be in favor of this