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PubMed2002

Membrane fatty acid unsaturation, protection against oxidative stress, and maximum life span: a homeoviscous-longevity adaptation?

Aging is a progressive and universal process originating endogenously that manifests during postmaturational life. Available comparative evidence supporting the mitochondrial free radical theory of aging consistently indicates that two basic molecular traits are associated with the rate of aging and thus with the maximum life span: the presence of low rates of mitochondrial oxygen radical production and low degrees of fatty acid unsaturation of cellular membranes in postmitotic tissues of long-lived homeothermic vertebrates in relation to those of short-lived ones. Recent research shows that steady-state levels of free radical-derived damage to mitochondrial DNA (mtDNA) and, in some cases, to proteins are lower in long- than in short-lived animals. Thus, nonenzymatic oxidative modification of tissue macromolecules is related to the rate of aging. The low degree of fatty acid unsaturation in biomembranes of long-lived animals may confer advantage by decreasing their sensitivity to lipid peroxidation. Furthermore, this may prevent lipoxidation-derived damage to other macromolecules. Taking into account the fatty acid distribution pattern, the origin of the low degree of membrane unsaturation in long-lived species seems to be the presence of species-specific desaturation pathways that determine membrane composition while an appropriate environment for membrane function is maintained. Mechanisms that prevent or decrease the generation of endogenous damage during the evolution of long-lived animals seem to be more important than trying to intercept those damaging agents or repairing the damage already inflicted. Here, the physiological meaning of these findings and the effects of experimental manipulations such as dietary stress, caloric restriction, and endocrine control in relation to aging and longevity are discussed.

Aging↗
PubMed1987

Canine pancreatic endocrine tumors: immunohistochemical analysis of hormone content and amyloid.

Thirty-one primary canine pancreatic endocrine tumors and their metastases were studied histologically and immunohistochemically for the presence of insulin, glucagon, somatostatin, pancreatic polypeptide (PP), gastrin, and adrenocorticotrophic hormone (ACTH). Tumors were also evaluated for the presence of amyloid. The cytoarchitectural pattern of 25 of 31 primary tumors was predominantly solid, whereas three tumors were mostly glandular, two were unclassified, and one had a gyriform pattern. Cells with insulin immunoreactivity were found in 30 of 31 tumors and were found in all cases in which there was clinical evidence of inappropriate insulin secretion. Insulin was the only hormone demonstrable in three of the 30 tumors, but cells immunoreactive for other hormones were also present in various combinations in most tumors [i.e., glucagon (13 of 30), somatostatin (17 of 30), PP (25 of 30), and gastrin (2 of 30)]. One tumor contained only cells with glucagon and PP immunoreactivity. Amyloid was found in ten of 31 primary tumors but was not detected in metastases. Cells with insulin immunoreactivity were the only cell type consistently present in tumors containing amyloid. Amyloid deposits did not immunoreact with any of the antisera. Seventeen of 31 dogs had metastasis of the pancreatic endocrine tumor to regional lymph nodes, liver, or both. All metastases available for study (15 of 17) contained cells with insulin immunoreactivity and some contained cells with PP or somatostatin immunoreactivity. No statistically significant (P greater than 0.05) differences in tendency to metastasize were found when pancreatic endocrine tumors were compared by region of origin, cytoarchitectural pattern, presence of amyloid, or by number of hormones contained within the tumor.

Adrenocorticotropic Hormone↗
PubMed2005

[The role of endoscopic ultrasound(EUS) in differential diagnosis of subepithelial oesophago-gastric lesions].

BACKGROUND: Endoscopic ultrasonography(EUS) allows high-resolution demonstration of the entire gut wall. The aim of the study was to clarify the usefulness of the EUS in differential diagnosis of upper gastro-intestinal subepithelail lesions(SEL). METHODS: From September 1998- March 2005, EUS was performed in 1600 patients. Among them, in 206pts (13%), this examination was carried out due to previous upper endoscopy, which revealed the suspicion to SEL or extraluminal compression. We studied the location, the size, echo pattern and originating layer of SEL. The results were compared with CT, angiography and operation with histology when possible. All EUS examinations were performed using Olympus GIF-130 videoecho-endoscope with 7,5/12MHz switchable radial probe. RESULTS: EUS accuracy in separating intramural masses from extraluminal compression was 96%(44/46). Among 160 pts with true SEL, in 95(59.3%), EUS revealed the existence of a stromal tumor arising from muscularis propria (92) or muscularis mucosae (3). The size of the tumor varied from 5-75mm; depth: 8-40mm. 33 patients were operated on. In 14/16(87%), the EUS diagnosis of benign stromal tumor was confirmed on operation. In 18/19(95%), EUS correctly disclosed the malignant tumor. EUS accuracy in predicting malignancy was 91.5%(32/35). Findings suggestive for malignancy were: size 40mm; inhomogenicity with microcysts and irregular outer margin. In 12 pts, EUS revealed lypoma. Abberant pancreas was correctly diagnosed in all 22pts. In 16 persons, EUS disclosed submucosal cysts: 6 of them were operated on and EUS diagnosis was confirmed in all. In 10 patients EUS visualized varices. The finding was confirmed on angiography. CONCLUSION: The EUS appears to be very effective in differential diagnosis of SEL in upper gastro-intestinal tract. Tumour size greater than 40mm, inhomomogenous echo pattern and irregular outer margin are very suggestive for malignancy.

Diagnosis, Differential↗
PubMed1996

The variable relationship between the lower cranial nerves and jugular foramen tumors: implications for neural preservation.

Tumors involving the jugular foramen (JF) have a variable relationship to the neurovascular structures (jugular vein, cranial nerves IX-XI) that traverse this conduit through the skull base. The surgeon familiar with the site of origin, growth pattern, and geometry of each of the common lesions affecting this region with respect to surrounding nerves and vessels is at a considerable advantage when undertaking a function-sparing procedure. Anatomically, the JF has two vascular compartments that may be affected by tumor: the jugular bulb laterally and a passage for the inferior petrosal sinus medially. Tumors may also penetrate the JF along the fibro-osseous diaphragm, which divides these two vascular channels. The lower cranial nerves lie on either side of this partition, which is connected to the posterior cranial fossa via a curved, funnel-shaped cone of dura. Tumors that arise within or penetrate the JF lateral to this neural plane displace the nerves medially, a position favorable for their preservation during tumor extirpation. By contrast, medially positioned tumors displace the cranial nerves onto the lateral tumor surface, where they interpose between surgeon and tumor-an unfavorable location. Glomus tumors consistently arise in the lateral aspect of the JF, displacing the lower cranial nerves medially. This positioning accounts for the high rate of neural preservation in small and medium-size glomus tumors that have not invaded the foramen's central partition. Meningiomas that arise lateral to the JF (e.g., the posterior petrous surface, sigmoid sinus) favorably displace the lower cranial nerves medially. By contrast, tumors that originate medial to the JF (e.g., clivus, foramen magnum) are unfavorable, laterally displacing the multiple small rootlets that coalesce into cranial nerves IX-XI into a vulnerable location. Schwannomas arise within the neural plane and have a variable geometry that depends, in part, upon the nerve of origin. Theoretically, tumors that arise from the ninth nerve, which is located on the lateral surface of the neural plane, should be more favorable than those originating from the tenth or eleventh nerves, which lie on its deep surface. The propensity of these three tumor types toward thrombosis of the jugulosigmoid complex also carries important surgical implications. Because glomus tumors arise from the jugular bulb, the jugulosigmoid complex is nearly always occluded. In both meningiomas and schwannomas, however, the jugular system may occasionally remain patent. This is important to recognize through angiography and/or magnetic resonance venography, since sacrifice of a patent, dominant system risks intracerebral venous infarction.

Brain↗
PubMed1997

Developmental age and taxonomic affinity of the Mojokerto child, Java, Indonesia.

An increasing number of claims place hominids outside Africa and deep in Southeast Asia at about the same time that Homo erectus first appears in Africa. The most complete of the early specimens is the partial child's calvaria from Mojokerto (Perning I), Java, Indonesia. Discovered in 1936, the child has been assigned to Australopithecus and multiple species of Homo, including H. modjokertensis, and given developmental ages ranging from 1-8 years. This study systematically assesses Mojokerto relative to modern human and fossil hominid growth series and relative to adult fossil hominids. Cranial base and vault comparisons between Mojokerto and H. sapiens sapiens (Hss) (n = 56), Neandertal (n = 4), and H. erectus (n = 4) juveniles suggest a developmental age range between 4 and 6 years. This range is based in part on new standards for assessing the relative development of the glenoid fossa. Regression analyses of vault arcs and chords indicate that H. erectus juveniles have more rounded frontals and less angulated occipitals than their adult counterparts, whereas Hss juveniles do not show these differences relative to adults. The growth of the cranial superstructures and face appear critical to creating differences in vault contours between H. erectus and Hss. In comparison with adult H. erectus and early Homo (n = 27) and adult Hss (n = 179), the Mojokerto child is best considered a juvenile H. erectus on the basis of synapomorphies of the cranial vault, particularly a metopic eminence and occipital torus, as well as a suite of characters that describe but do not define H. erectus, including obelion depression, supratoral gutter, postorbital constriction, mastoid fissure, lack of sphenoid contribution to glenoid fossa, and length and breadth ratios of the temporomandibular joint. Mojokerto is similar to other juvenile H. erectus in the degree of development of its cranial superstructures and its vault contours relative to adult Indonesian specimens. The synapomorphies which Mojokerto shares with H. erectus are often considered autapomorphies of Asian H. erectus and confirm the early establishment and long-term continuity of the Asian H. erectus bauplan. This continuity does not, however, necessarily reflect on the pattern of origin of modern humans in the region.

Adolescent↗
PubMed1999

Projection patterns of single mossy fibers originating from the lateral reticular nucleus in the rat cerebellar cortex and nuclei.

Projection of neurons in the lateral reticular nucleus (LRN) to the cerebellar cortex (Cx) and the deep cerebellar nuclei (DCN) was studied in the rat by using the anterograde tracer biotinylated dextran amine (BDA). After injection of BDA into the LRN, labeled terminals were seen bilaterally in most cases in the vermis, intermediate zone, and hemisphere of the anterior lobe, and in various areas in the posterior lobe, except the flocculus, paraflocculus, and nodulus. Areas of dense terminal projection were often organized in multiple longitudinal zones. The entire axonal trajectory of single axons of labeled LRN neurons was reconstructed from serial sections. Stem axons entered the cerebellum through the inferior cerebellar peduncle (mostly ipsilateral), and ran transversely in the deep cerebellar white matter. They often entered the contralateral side across the midline. Along the way, primary collaterals were successively given off from the transversely running stem axons at almost right angles to the Cx and DCN, and individual primary collaterals had longitudinal arborizations that terminated as mossy fibers in multiple lobules of the Cx. These collaterals arising from single LRN axons terminated bilaterally or unilaterally in the vermis, intermediate area, and sometimes hemisphere, and in different cerebellar and vestibular nuclei simultaneously. The cortical terminals of single axons appeared to be distributed in multiple longitudinal zones that were arranged in a mediolateral direction. All of the LRN axons examined (n = 29) had axon collaterals to the DCN. All of the terminals observed in the DCN and vestibular nuclei belonged to axon collaterals of mossy fibers terminating in the Cx.

Animals↗
PubMed2000

Two-dimensional gel analysis of the proteome of lager brewing yeasts.

Modern lager brewing yeasts used in beer production are hybrid strains consisting of at least two different genomes. To obtain information on the identity of the parental strains that gave rise to industrial lager yeasts, we used two-dimensional (2-D) gel electrophoresis and analysed the proteomes of different Saccharomyces species isolated from breweries. We found that the proteome of lager brewing yeasts and of the type strains of S. carlsbergensis, S. monacensis and S. pastorianus can be interpreted as the superimposition of two elementary patterns. One originates from proteins encoded by a S. cerevisiae-like genome. The other corresponds to a divergent Saccharomyces species whose best representative is a particular S. pastorianus strain, NRRL Y-1551. A map of industrial lager brewing yeasts has been established, with the individual origin of proteins and with identification of protein spots by comparison to known S. cerevisiae proteins. This 2-D map can be accessed on the Lager Brewing Yeast Protein Map server through the World Wide Web. This study provides the first example of the use of proteome analysis for investigating taxonomic relationships between divergent yeast species.

Amino Acid Sequence↗
PubMed1999

Lymphoepithelioma-like carcinoma of the skin with apparent origin in the epidermis--a pattern or an entity? A case report.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is prototypically represented by "undifferentiated" nasopharyngeal carcinoma, but it has also been described in many other anatomic locations, including the skin. In the last of these sites, primary LELC has been assumed in the past to show dermal adnexal differentiation. METHODS: The authors present a case wherein LELC of the skin (LELCS) instead appeared to be a morphologic manifestation of squamous carcinoma of the skin surface, as supported by the results of immunohistology and in situ hybridization. RESULTS: Like other examples of LELCS, it showed no evidence of integration of the Epstein-Barr viral genome, and its behavior was indolent. CONCLUSIONS: The heterogeneous nature of LELC as seen in different body sites is reviewed in this report, resulting in the conclusion that this tumor probably represents a morphologic pattern rather than a distinct clinicopathologic entity.

Aged↗
PubMed1998

The geography of Bangladeshi migration to Rome.

"With reference to the Bangladeshi community in Rome, this paper provides some answers to three key geographical questions: what is the migrants' regional pattern of origin in their home country; what are the mechanisms and routes of their migration to Italy; how are they spatially distributed in Rome?... Chain migration links specific origins in Bangladesh with spatial clusters and economic activities in Rome; the key here is the role of Bangladeshi community leaders in Rome who act both as migration sponsors and entrepreneurs."

Asia↗
PubMed1982

Changes in the location and type of gastric adenocarcinoma.

To document our impression of major changes in aspects of gastric adenocarcinoma, we reviewed and compared 62 consecutive cases from 1975 through 1978 and 31 cases from 1938 through 1942. The average age at diagnosis increased from 58 to 68 years, the male to female ratio decreased to approximately 1:1, and carcinomas composed predominantly (50% or more) of signet-ring cells (SRC) increased from 9 to 39% of the total cases. In the recent series, carcinomas with SRC (compared with those without SRC) occurred nine years earlier, were more frequent in women, were located distally, and had an infiltrative growth pattern. Carcinomas originating in the proximal stomach (cardia) were not noted in the old series but formed 27% of the recent cases. These tumors showed a male predominance, contained SRC less often, and were less commonly associated with chronic gastritis. The implications of these observations are discussed.

Adenocarcinoma↗
PubMed1993

Splenic metastasis in hairy cell leukemia.

BACKGROUND: Splenic metastasis is uncommon and usually occurs in the setting of widespread visceral metastasis. Splenic metastasis as an initial manifestation of disease and sole site of metastasis has not been reported previously. METHODS: The authors describe a patient with hairy cell leukemia (HCL) with the unexpected finding of metastatic adenocarcinoma in the spleen. Direct inspection at the time of laparotomy and subsequent radiographic studies did not show a primary or additional metastatic tumor. Eventually, he manifested evidence of pulmonary and hepatic metastases and died with fungal sepsis. RESULTS: The splenectomy specimen showed HCL and metastatic adenocarcinoma. Immunohistochemical studies showed adenocarcinoma with diffuse cytoplasmic staining for prostate-specific antigen and focally positive results with prostatic acid phosphatase antigen. Postmortem examination 9 months later showed HCL and widespread metastatic adenocarcinoma. No primary tumor was identified, and multiple tissue blocks of the prostate had negative findings for tumor. CONCLUSIONS: The immunohistologic features of the metastatic adenocarcinoma were interpreted as prostatic in origin. The pattern of isolated metastatic disease in the absence of primary tumor appears to represent another possible atypical disease presentation of prostatic cancer. Hairy cell-induced structural and immunologic alterations within the splenic microenvironment may have contributed to this unique clinical presentation.

Adenocarcinoma↗
PubMed1980

Torsion dystonia in Israel.

A country-wide search for idiopathic torsion dystonia (ITD) in Israel between 1969 and 1975 revealed 42 patients (41 Jewish and 1 Druze Arab). Prevalence of ITD per million population, age-adjusted to the United States population in 1970, was 10.8 in the total Jewish population (22.0 among Jews of European extraction contrasted with 1.5 among Jews with Afro-Asian forebears). Among Europeans, the highest prevalence was among Jews from Eastern Europe. The average age-adjusted annual incidence rates per million population were 0.43 in the total Jewish population, 0.98 in the Europeans, and 0.11 in the Afro-Asians. Among the 40 patients for whom familial data were available, the majority of cases (26) were sporadic. The other 14 belonged to four unrelated European families, all of Russian-Polish origin. The pattern of inheritance in these four families fits an autosomal dominant model with incomplete penetrance.

Adolescent↗
PubMed2004

Adult human mylohyoid muscle fibers express slow-tonic, alpha-cardiac, and developmental myosin heavy-chain isoforms.

Some adult cranial muscles have been reported to contain unusual myosin heavy-chain (MHC) isoforms (i.e., slow-tonic, alpha-cardiac, embryonic, and neonatal), which exhibit distinct contractile properties. In this study, adult human mylohyoid (MH) muscles obtained from autopsies were investigated to detect the unusual MHC isoforms. For comparison, the biceps brachii and masseter muscles of the same subjects were also examined. Serial cross-sections from the muscles studied were incubated with a panel of isoform-specific anti-MHC monoclonal antibodies that distinguish major and unusual MHC isoforms. On average, the slow type I and fast type II MHC-containing fibers in the MH muscle accounted for 54% and 46% of the fibers, respectively. In contrast to limb and trunk muscles, the adult human MH muscle was characterized by a large proportion of hybrid fibers (85%) and a small percentage of pure fibers (15%; P < 0.01). Of the fast fiber types, the proportion of the type IIa MHC-containing fibers (92%) was much greater than that of the type IIx MHC-containing fibers (8%; P < 0.01). Our data demonstrated that the adult human MH fibers expressed the unusual MHC isoforms that were also identified in the masseter, but not in the biceps brachii. These isoforms were demonstrated by immunocytochemistry and confirmed by electrophoretic immunoblotting. Fiber-to-fiber comparisons showed that the unusual MHC isoforms were coexpressed with the major MHC isoforms (i.e., MHCI, IIa, and IIx), thus forming various major/unusual (or m/u) MHC hybrid fiber types. Interestingly, the unusual MHC isoforms were expressed in a fiber type-specific manner. The slow-tonic and alpha-cardiac MHC isoforms were coexpressed predominantly with slow type I MHC isoform, whereas the developmental MHC isoforms (i.e., embryonic and neonatal) coexisted primarily with fast type IIa MHC isoform. There were no MH fibers that expressed exclusively unusual MHC isoforms. Approximately 81% of the slow type I MHC-containing fibers expressed slow-tonic and alpha-cardiac MHC isoforms, whereas 80% of the fast type IIa MHC-containing fibers expressed neonatal MHC isoform. The m/u hybrid fibers (82% of the total fiber population) were found to constitute the predominant fiber types in the adult human MH muscle. At least seven m/u MHC hybrid fiber types were identified in the adult human MH muscle. The most common m/u hybrid fiber types were found to be the MHCI/slow-tonic/alpha-cardiac and MHCIIa/neonatal, which accounted for 39% and 33% of the total fiber population, respectively. The multiplicity of MHC isoforms in the adult MH fibers is believed to be related to embryonic origin, innervation pattern, and unique functional requirements.

Electrophoresis↗
PubMed2005

DNA methylation in mammalian development and disease.

Epigenetic modification of the cytosine base of DNA by its methylation introduced the possibility that beyond the inherent information contained within the nucleotide sequence there was an additional layer of information added to the underlying genetic code. DNA methylation has been implicated in a wide range of biological functions, including an essential developmental role in the reprogramming of germ cells and early embryos, the repression of endogenous retrotransposons, and a generalized role in gene expression. Special functions of DNA methylation include the marking of one of the parental alleles of many imprinted genes, a group of genes essential for growth and development in mammals with a unique parent-of-origin expression pattern, a role in stabilizing X-chromosome inactivation, and centromere function. In this regard, it is not surprising that errors in establishing or maintaining patterns of methylation are associated with a diverse group of human diseases and syndromes.

Alleles↗
PubMed2005

A mathematical model of N-linked glycosylation.

Metabolic engineering of N-linked oligosaccharide biosynthesis to produce novel glycoforms or glycoform distributions of a recombinant glycoprotein can potentially lead to an improved therapeutic performance of the glycoprotein product. A mathematical model for the initial stages of this process, up to the first galactosylation of an oligosaccharide, was previously developed by Umana and Bailey (1997) (UB1997). Building on this work, an extended model is developed to include further galactosylation, fucosylation, extension of antennae by N-acetyllactosamine repeats, and sialylation. This allows many more structural features to be predicted. A number of simplifying assumptions are also relaxed to incorporate more variables for the control of glycoforms. The full model generates 7565 oligosaccharide structures in a network of 22,871 reactions. Methods for solving the model for the complete product distribution and adjusting the parameters to match experimental data are also developed. A basal set of kinetic parameters for the enzyme-catalyzed reactions acting on free oligosaccharide substrates is obtained from the previous model and existing literature. Enzyme activities are adjusted to match experimental glycoform distributions for Chinese Hamster Ovary (CHO). The model is then used to predict the effect of increasing expression of a target glycoprotein on the product glycoform distribution and evaluate appropriate metabolic engineering strategies to return the glycoform profile to its original distribution pattern. This model may find significant utility in the future to predict glycosylation patterns and direct glycoengineering projects to optimize glycoform distributions.

Animals↗
PubMed1992

A morphological correlate of target recognition by regenerating motor axons in the cockroach.

A specific cell recognition process during regeneration of severed axons of identified cockroach motor neurons eventually leads to the reformation of the original innervation pattern of target muscles in the leg. This occurs even though, at early times after nerve crush, the multiple branches of each regenerating axon grow into both appropriate and inappropriate muscles. In this study, we sought to examine whether there are any structural differences between regenerating axon branches in appropriate and inappropriate muscles that could lead to an understanding of why only those in inappropriate muscles are eliminated. A neuron subset-specific monoclonal antibody, NSS-2A, which labels the inhibitory motor neurons, was used to make their axon branches visible at various times after nerve crush. In inappropriate muscles, these axons grow primarily parallel to the muscle fibers and are later eliminated. In the appropriate muscles, these axon branches initially also grow parallel to the muscle fibers, but subsequently grow many interstitial collaterals. The formation of the collateral branches is a morphological correlate of the specific interaction of a neuron with its appropriate muscle. The simultaneous occurrence of axonal elimination and collateral sprouting supports the idea that the two processes are causally related, as suggested by the sibling neurite bias hypothesis.

Animals↗
PubMed1986

T cell nature of some lymphokine-activated killer (LAK) cells. Frequency analysis of LAK precursors within human T cell populations and clonal analysis of LAK effector cells.

The cell lineage of the lymphokine-activated killer (LAK) cells has been reinvestigated. Both T and non-T cells, isolated on the basis of rosette formation with sheep erythrocytes (E), generated LAK activity after 3-4 days of culture in recombinant interleukin 2 (rIL 2) in 8 different individuals tested. By applying a microculture technique which allows clonal expansion of virtually all E rosetting T cells, we further analyzed the frequency of clonogenic LAK precursors within T cell populations. Approximately 1 of 25 T cells was found to be a LAK precursor. Moreover, microcultures with LAK activity lysed both the natural killer-sensitive K562 cell line and the P815 target cells in the presence of phytohemagglutinin (PHA). Since cytolytic T lymphocytes capable of lysing P815 cells in the PHA-dependent assay were approximately 1/3, it is evident that only a minor subset of cytolytic T lymphocyte precursors can acquire LAK activity even in the presence of large amounts of IL 2. Several LAK clones obtained by limiting dilution were further expanded and analyzed for their phenotypic and functional properties. Twelve out of 14 clones analyzed expressed the T3+ T11+ phenotype whereas 2 were T3- T11+. All had maintained their original cytolytic pattern; moreover, the large majority of the T3+ clones produced IL 2 and interferon-gamma following PHA stimulation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1983

Immunoglobulin gene organisation and expression in haemopoietic stem cell leukaemia.

We have analysed the organisation and expression of mu genes in the granulocytic phase and in the lymphoid and myeloid blast crises of Philadelphia chromosome (Ph1) chronic granulocytic leukaemia (CGL), a leukaemia which is known to arise in multipotential stem cells. We find that mu chain gene rearrangement occurs exclusively in lymphoid blast crisis leading in some, but not all, cases to the synthesis of small amounts of cytoplasmic mu chains characteristic of early pre-B lymphocytes. In Southern blots, only one or two rearranged mu chain genes are seen, suggesting that a clonal event leading to blast crisis can occur in a committed B cell precursor rather than in the multipotential stem cell precursor, in which the Ph1 chromosome originated. The pattern of mu gene rearrangement observed in Ph1 CGL blast crisis is compared with that in normal B cells, other B lineage malignancies, myeloid leukaemias and T cell leukaemias.

B-Lymphocytes↗