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Biomedical subjects

A Baruch

Publications and source records attributed to A Baruch.

16 recordsLinked to original sources
PubMed1995

Developmental regulation of the ovine beta-lactoglobulin/human serum albumin transgene is distinct from that of the beta-lactoglobulin and the endogenous beta-casein genes in the mammary gland of transgenic mice.

We compared the developmental pattern of expression of the sheep beta-lactoglobulin (BLG), the chimeric BLG/human serum albumin (HSA), and the endogenous murine beta-casein genes in the mammary gland of virgin, pregnant and lactating transgenic mice, both at the RNA (expression) and protein (synthesis and secretion) levels. The BLG and casein genes were expressed at very low levels in virgin animals and during early stages of pregnancy. The increase in the expression of these genes started at the second half of pregnancy and reached a peak between the end of pregnancy and day 10 of lactation. The accumulation of their RNA coincided with that of the corresponding proteins, indicating a transcriptional control of expression of these genes. The expression and secretion patterns of the endogenous casein gene in transgenic and nontransgenic mice were indistinguishable. The hybrid BLG/HSA gene constructs displayed distinct patterns of expression in virgin animals and at early stage of pregnancy, from that of the BLG transgene or the endogenous mouse milk protein gene. High levels of expression (17-60% of that on day 18 of pregnancy) were detected in the mammary gland of virgin animals. At day 5 of pregnancy there was a dramatic decrease in HSA synthesis and secretion in all transgenic strains tested. The down-regulation, revealed by immunoprecipitation and immunohistochemical studies, demonstrated that at that stage of pregnancy only 10-18% of ductal structures contained HSA expressing cells in contrast to the majority of ducts expressing HSA in virgin animals. These morphological studies also demonstrated that the down-regulation in HSA synthesis and secretion was correlated with the transition from ducts comprised of a single layer of epithelial cells (characteristic of the virgin state) to ducts composed of multilayers of such cells. In two of the three transgenic strains tested, the down-regulation at the protein level was associated with a similar decrease in HSA transcripts. In the exceptional strain no. 23, HSA transcripts continued accumulating even at this stage. The differences in the control of expression at the RNA level between these transgenic strains were also confirmed by in situ hybridization. Our results suggest the involvement of at least two regulatory mechanisms effective at early stages of gestation in the control of expression/secretion of the HSA transgene targeted for expression in the mammary gland by the BLG milk protein promoter. These putative mechanisms may play key roles in the interplay between normal mammogenesis and lactogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Tyrosine phosphorylation of the MUC1 breast cancer membrane proteins. Cytokine receptor-like molecules.

Phosphorylation on tyrosine residues is a key step in signal transduction pathways mediated by membrane proteins. Although it is known that human breast cancer tissue expresses at least 2 MUC1 type 1 membrane proteins (a polymorphic high molecular weight MUC1 glycoprotein that contains a variable number of tandem 20 amino acid repeat units, and the MUC1/Y protein that is not polymorphic and is lacking this repeat array) their function in the development of human breast cancer has remained elusive. Here it is shown that these MUC1 proteins are extensively phosphorylated, that phosphorylation occurs primarily on tyrosine residues and that following phosphorylation the MUC1 proteins may potentially interact with SH2 domain-containing proteins and thereby initiate a signal transduction cascade. As with cytokine receptors, the MUC1 proteins do not harbor intrinsic tyrosine kinase activity yet are tyrosine phosphorylated and the MUC1/Y protein participates in a cell surface heteromeric complex whose formation is mediated by two cytoplasmically located MUC1 cysteine residues. Furthermore, the MUC1/Y protein demonstrates sequence similarity with sequences present in cytokine receptors that are known to be involved in ligand binding. Our results demonstrate that the two MUC1 isoforms are both likely to function in signal transduction pathways and to be intimately linked to the oncogenetic process and suggest that the MUC1/Y protein may act in a similar fashion to cytokine receptors.

3T3 Cells↗
PubMed1994

Characterization and molecular cloning of a novel MUC1 protein, devoid of tandem repeats, expressed in human breast cancer tissue.

The human breast cancer marker protein, MUC1, is a polymorphic transmembrane molecule containing a large extracellular domain that is primarily composed of a variable number of highly conserved 20-amino-acid tandem repeats. We report here the detection of a novel invariantly sized 1.2-kb MUC1 mRNA, in addition to the large polymorphic mRNAs, by probing Northern blots with MUC1-cDNA-unique-sequence probes. The nucleotide sequence of this novel MUC1 mRNA demonstrates that it is identical to the MUC1 cDNA sequences downstream and upstream to the tandem-repeat array of the transmembrane form of MUC1. However, it contains neither the central tandem repeat array itself nor its directly flanking sequences that are deleted by a differential splicing event utilizing splice acceptor and donor sequences 5' and 3' to the tandem-repeat array. The splice event retains, downstream to the splice acceptor site, an open reading frame identical to that of the repeat-array-containing MUC1 thereby generating the novel MUC1/Y protein. Cells transiently transfected with the novel MUC1/Y cDNA express the MUC1/Y protein that is modified by glycosylation. The MUC1/Y protein is also readily detected in human breast cancer cells grown in vitro. Furthermore, primary breast cancer tissue samples demonstrate significant levels of the MUC1/Y protein whereas expression in tissue adjacent to the tumor is undetectable. Molecular characterization presented here, of the novel MUC1/Y molecule lacking the repeat array, suggests that it is likely to play a role distinct to that of the polymorphic repeat-array-positive MUC1 protein and that it may act as a new marker protein for human breast cancer.

Amino Acid Sequence↗
PubMed1994

Does a novel form of the breast cancer marker protein, MUC1, act as a receptor molecule that modulates signal transduction?

Molecular analysis of a protein highly expressed in human breast cancer, indicates the presence of a polymorphic tandem repeat domain that encodes a conserved 20 amino acid repeat motif rich in serine and threonine residues that in the mature protein, designated MUC1, are linked via O-glycosidic linkages to sugar residues. Recent studies performed in our laboratory have led to the molecular characterization of a novel MUC1 repeat array minus mRNA, generated by an alternative splicing event that deletes the central tandem repeat array and its flanking sequences. The conceptually derived amino acid sequence of the novel MUC1 protein shows that it is identical with the previously reported transmembrane MUC1 amino acid sequence except for the deletion of the central 20 amino acid tandem repeat array and sequences immediately flanking the repeat array. This indicates that the novel MUC1 protein, which is devoid of the "hallmark" feature of mucins, the tandem repeat array, may be functionally different to the much larger, heavily glycosylated polymorphic repeat array containing MUC1 proteins, that affect cell-cell interactions. Based on an analysis of its peptide sequence, we propose the hypothesis that the novel MUC1 protein may act as a receptor molecule that modulates signal transduction. Preliminary experimental data supports this hypothesis. It appears, therefore, that the MUC1 gene is multifunctional with regard to its protein products- the repeat array containing MUC1 proteins may alter cellular adhesion processes whereas the novel MUC1 protein could be acting as a receptor-like molecule participating in signal transmission.

Amino Acid Sequence↗
PubMed1987

Simple bone cyst of the metacarpal.

Simple bone cyst is a benign tumor-like lesion that occurs principally in the humerus and the femur. Occurrence within the hand is rare and involvement of the metacarpals is even more uncommon. Two similar cases of a simple bone cyst affecting the metacarpals were treated by complete excision of the cyst and replacement by a cortico-medullar autogenous graft.

Bone Cysts↗
PubMed1982

The cytoarchitecture of the dorsal cochlear nucleus in the 3-month- and 26-month-old C57BL/6 mouse: a Golgi impregnation study.

The cytoarchitecture of the dorsal cochlear nucleus (DCN) was compared in 3- and 26-month-old C57BL/6 mice. The effects of genetically controlled progressive hearing loss present in the CNS in this mouse strain were analyzed with Nissl-stained and Golgi-impregnated material. The DCN was divided into the superficial molecular, an intermediate fusiform-granule, and the deep polymorphic layers. The molecular layer (ML) consisted of many fibers and a few small ovoid to spherical, fusiform, and granule cells. The fusiform-granule layer (FL) contained large fusiform and many granule cells. Most FL fusiform cells were oriented with their long axes perpendicular to the DCN surface and were present as small aggregations or individually. Cartwheel cells were adjacent to the FL fusiform cells. The deep polymorphic layer (PL) contained spherical, fusiform, granule, and multipolar neurons. The granule cells formed a dorsal cap of the DCN. From this cap, sheets of granule cells separated the DCN from the posterior ventral cochlear nucleus (PVCN) and from the brainsteM. The internal organization, neuronal location, orientation, and morphology were similar in both age groups. The granule cells had four to five primary dendrites, varicosities, and few to no dendritic appendages. The FL fusiform cells displayed different dendritic morphology in the two ages. One or two elaborate primary ML apical dendrites in the 3-month-old mice were covered with spikelike dendritic spines. The basal one or two PL dendrites were less elaborate and had few dendrite spines. In contrast, FL fusiform neurons in 26-month-old mice had regular dendritic varicosities and fewer spines which were short and stumpy. Basal dendrites had varicosities and interruptions. Cartwheel neurons in 3-month-old mice had elaborate ML dendritic trees covered with dendritic spines. In 26-month-old mice the dendrites had many varicosities and fewer short blunted dendritic spines. Large multipolar neurons in older mice had thinner dendrites with more varicosities than were in the 3-month group. In both age groups multipolar cells had few dendritic spines limited distally. Small and large spherical cells had two to five primary dendrites with varicosities, little higher-order branching, and spines. Fusiform cells had one or two primary dendrites, little secondary branching, and few to no spines. Minor degenerative changes were noted in spherical and fusiform cells in the two age groups. These included dendritic varicosities, interruptions, and some irregularities of somata surface. Degenerative changes present in the cochlea had significant effects on a limited population of DCN neurons. Finally, the neuronal morphology and architecture of the DCN in C57BL/6 mouse is similar to other mammalian species.

Animals↗
PubMed1980

Angulated bone peg.

The use of an angulated bone peg in arthrodesis of a digital joint is presented. The technique was demonstrated in two patients with severe bone loss. A bone graft was fashioned into an angulated peg of the desired angle and size and inserted in both sides of the gap. The suggested technique preserves the finger's length, maintaining the necessary angulation, and provides adequate fixation.

Adult↗
PubMed1979

Distraction-lengthening of digital rays in the management of the injured hand.

The distraction-lengthening principle and apparatus, formerly used in the hand for reconstruction in congenital anomalies and traumatic amputations, is described for reconstruction of metacarpals and phalanges shortened by injuries, especially gunshot wound, where those bones have lost significant length. Hands in which single metacarpals have been shortened or in which multiple digits are involved may benefit from the technique.

Adult↗
PubMed1977

False aneurysm of the digital artery.

A case of false aneurysm of the digital artery is described. To the best of our knowledge it is the first reported case of false aneurysm involving the thumb. The aetiological factors which are usually responsible for the development of a false aneurysm are briefly discussed. The most common factor seems to be a direct injury of the arterial wall by a sharp tool and continuing flow of the blood in the artery. Although the fingers are commonly exposed to injuries with sharp tools, development of a false aneurysm in them seems to be extremely rare.

Adult↗
PubMed1976

Osteoarthritis at the base of the thumb. The concept of monoarticular reconstruction.

Osteoarthritic affection of the base of the thumb involving 148 hands has been studied. Isolated osteoarthritis of the trapezio-metacarpal joint was found to be the largest group including a total of 111 hands. Reconstruction of this particular joint by a new technique is described and long-term results reported. A small series of isolated osteoarthritis of the trapezio-scaphoid joint is presented and reconstruction by replacing the affected articular surface of the carpal scaphoid is described. Osteoarthritic involvement of more than one of the articular surfaces of the trapezium was found in a group of 31 hands. In all of them the trapezio-metacarpal joint was predominantly affected. The rationale for monoarticular reconstruction of the trapezio-metacarpal joint, regardless of the extent of involvement, is discussed in detail.

Adult↗