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The Institute for Scientific Information (ISI), a database publishing company that publishes Current Contents and Science Citation Index, has devised and promulgated what it terms the journal "impact factor." ISI describes this factor as a "measure of the frequency with which the 'average article' in a journal has been cited in a particular year." The factor is a ratio between citations and recent citable published items calculated by dividing the number of all current citations of items published in a journal during the preceding 2 years by the number of articles published in those 2 years by that journal. What, if anything, is wrong with the "impact factor"? There is absolutely nothing incorrect with the calculation of the ratio itself. However, the "impact factor" is misnamed and misleading. Being misnamed and misleading, the "impact factor" has been misused. It is being held out as a measure of the importance of a specific journal article and the journal in which the article appeared. By extension, the "impact factor" is also being misused to gauge the relative importance of individual researchers, research programs, and even the institution hosting the research. We recommend that the term "impact factor" be abolished and that this measure be renamed in keeping with its actual role, that merely of a time-specific "citation rate index" and nothing more. What is currently called the "impact factor" should not be misused to evaluate journals or to validate the scientific relevance of a particular researcher or research program, especially in decisions regarding employment, funding, and tenure.

The t(14;19)(q32.3;q13.1) is a recurring translocation found in the neoplastic cells of some patients with chronic lymphocytic leukemia (CLL) or other B-lymphocytic neoplasms. We previously cloned the translocation breakpoint junctions present in the leukemic cells from three such patients and identified a gene, BCL3, whose transcription is increased as a result of the translocation. In the present paper, we describe three additional patients with the t(14;19), one with lymphoma and two with CLL, and report the cloning and sequencing of the breakpoint junction in one of these patients as well as in a previously reported patient. We and others have found that the breakpoints on chromosome 14, with one exception, fall within the switch region upstream of the immunoglobulin heavy chain C alpha 1 or C alpha 2 sequences. Several of the breaks within chromosome 19 fall immediately upstream of the BCL3 gene, but several others are more than 16 kb 5' of the gene. Most patients with CLL and the t(14;19) also show trisomy 12.

FRA11A, a rare folate-sensitive fragile site assigned to 11q13.3, lies in an area of genomic instability associated with several diseases and amplification events. To map FRA11A, we used fluorescence in situ hybridization with yeast artificial chromosome and cosmid probes on metaphase chromosomes of patients expressing the fragile site. FRA11A was found situated centromeric to ACTN3 and telomeric to D11S913, these markers being within an interval of approximately 1 Mb in the 11q13.3 region.

Autosomal chromosome abnormalities are far from always detectable and, when detected, far from fully consistent in malignant gliomas. In 15 of 41 malignant gliomas, we found autosomal chromosome aberrations ranging from solitary trisomy to a wildly abnormal polyploid complement. The sequence of chromosome events appears to proceed from the normal to the near-diploid state (via structural and numerical changes) to near-tetraploidy (via polyploidization), and finally toward near-triploidy (via chromosome loss and additional rearrangements). Characteristic chromosome changes of trisomy 7 and monosomy 10 were repeatedly found, usually together in the same cell clones. In only one case was trisomy 7 an isolated change. We observed structural rearrangements of chromosomes 7 and 10 which may be of some use in mapping specific genes duplicated or deleted by the whole-chromosome changes of chromosomes 7 and 10. Nonrandom structural changes of other autosomes, including chromosomes 1, 5, and 11, fit with the model of malignant glioma as a process involving multiple genes. An unusual concentration of breakpoints in 12q13, juxtaposing it to at least five other regions, reflects the presence of genetic information in 12q13 important to the development of malignant gliomas.

Sex chromosomal monosomy with total loss of an X or Y is frequently observed in malignant gliomas. Beyond that, not much is known about the behavior of the sex chromosomes in these tumors. We noted loss of the X from 3 of 13 gliomas from women (23%) compared to loss of the Y from 16 of 28 gliomas from men (57%). There were two structural rearrangements of the Y (an inversion and a translocation with chromosome 4). Most unexpectedly, clones with sex chromosome reversal were encountered in 3 cases. These XX clones in gliomas from men are perforce the consequence of Y loss coupled with X isodisomy, a nonrandom sequence of sex chromosome changes. We examined the company kept by numerical X and Y changes in clones and found that clones with numerical sex chromosome changes had fewer autosomal abnormalities, reflecting a distinct tendency to clonal separation of sex chromosome from autosomal abnormalities. We conclude that the sex chromosome changes are not a necessary part of the neoplastic process in malignant gliomas but that they must be of biologic significance to the brain since they are highly nonrandom in frequency, type, and sequence in brain cells.

Gliomatosis cerebri is a rare brain tumor which histologically resembles a diffuse cerebral astrocytoma. It can simultaneously infiltrate multiple sites in the cerebrum, cerebellum, brainstem, and spinal cord. This remarkable diffuseness has led to the idea that gliomatosis cerebri does not derive from a solitary focus but must arise from a broad field of glial cells. We studied the chromosomes from gliomatosis cerebri in a 12-year-old boy by conventional cytogenetics and fluorescence in situ hybridization (FISH). Aside from normal cells, we found a majority of cells with the karyotype 44,XY,del(6)(q25),del(14)(q21), der(15;21)(q10;q10),add(18)(q22),del(19)(p12),add(20)(p13),-21. A smaller proportion of cells had 88 chromosomes with a doubling of this abnormal karyotype. These findings are consistent with a clonal neoplasm stemming from a single cell. The chromosome changes we observed, with the possible exception of the chromosome 6 deletion, did not resemble those frequently found in astrocytomas. Gliomatosis cerebri may therefore belong to a separate category of brain tumors.

We present prenatal diagnosis and follow-up examination of an individual with a de novo paracentric inversion of the long are of chromosome 14. A literature search documented 19 other cases of paracentric inversion of 14q. The outcome of each of these cases is specified together with that of this current case. Four of the 20 cases, all XY, manifested significant abnormalities with mental retardation and microcephaly present in 3 of the 4 cases; 15% (2/13) of familial cases had abnormalities and 40% (2/5) of de novo cases had abnormalities.

Myotonic dystrophy (DM) arises from an unstable trinucleotide (CTGn) repeat sequence within the DM locus at 19q13.3. Twenty-three myotonic dystrophy families containing 205 persons with no symptoms, minimal manifestations, classic DM or congenital DM were investigated to validate the application of the pM10M6 probe to direct molecular diagnosis. Affected family members had been diagnosed clinically and the unaffected family members had been assigned carrier probabilities close to either zero or 100%, using closely linked flanking markers. Southern analysis identified all 89 DM gene carriers as having expansions of the unstable element. PstI detected all small expansions of the repeat sequence as easily seen discrete bands; but large expansions were usually seen as diffuse smears, sometimes difficult to distinguish from lane background. EcoRI concentrated these diffuse smears, associated with somatic instability, into discrete bands which were easy to detect; but it did not resolve the smaller expansions present in 9 (10%) of the DM carriers. It is essential that PstI and EcoRI gels are run in parallel to detect all DM gene carriers. The extent of expansion of CTG correlated with age of onset and disease severity. Biopsies of various fetal tissues from two terminated pregnancies confirmed the diagnosis obtained by CVS and revealed no heterogeneity between tissues at this developmental stage. Further expansion occurred during the culture of CVS cells, indicating that direct prenatal diagnosis needs to be carried out on CVS tissue rather than on cultured cells. The intergenerational change of the repeat sequence from DM parent to DM offspring showed a significant parental sex difference for those parents with large expansions. Contraction of the unstable element was observed in the three males carrying the largest expansions and could explain why congenital DM is exclusively of maternal origin.

A case of congenital acute lymphoblastic leukemia (ALL) displayed an X;6 translocation. This is the third reported case of ALL with an X;6 translocation. In addition, two of the three ALL cases occurred during infancy, at ages 2 months and newborn, and both translocations involved the band q15-16 region of chromosome 6. Anomalies of the long arm of chromosome 6, mainly interstitial and terminal deletions, have been reported as a recurrent karyotypic event in a significant number of ALL cases. The molecular basis and propensity of an X;6 rearrangement in this case of congenital ALL is unclear and merits further investigation. The similarities in this case and the other infant ALL case cited suggest that an X;6 rearrangement with a breakpoint in bands q15-16 of chromosome 6 is characteristic of a form of congenital ALL.

One gauge of creativity in medical genetics and dysmorphology is the eponym. Conditions named for people reflect their powers of observation and analysis. We examined the fields and ages of 210 eponymous physicians and scientists whose biographies were published by Peter and Greta Beighton [1986] in The Man Behind the Syndrome. Twenty fields were represented with the dominant fields being, in order, pediatrics, neurology, general and internal medicine, pathology, radiology, and orthopedics. The ages of the eponymous workers averaged 43 years at the time of their relevant publications. Fully a fifth of the contributions were made by persons aged 30 years or less, or 60 years or more, suggesting that eponymous fame may come to workers of talent independent of age.

A gene locus for ataxia-telangiectasia (A-T) is in chromosome region 11q22 to 11q23 and predisposes to cancer. Ataxia-telangiectasia patients appear to have two separate clinical patterns of malignancy. One pattern involves solid tumors, which have not been stressed and which include malignancies in the oral cavity, breast, stomach, pancreas, ovary, and bladder. Detection of a solid tumor in an A-T patient should serve as a warning. It heralds a markedly elevated risk of another malignancy in that patient. The second pattern of neoplasia in A-T is well recognized and consists of lymphocytic leukemia and non-Hodgkin's lymphoma. These malignancies may relate to immunodeficiency in A-T and to chromosome breakage and rearrangement, which are a feature of A-T. These two patterns of malignancy may be truly separate and reflect different mechanisms of malignancy in A-T, or they may not really be separate but instead reflect a single mechanism of malignancy. The situation in A-T is reminiscent of that in the acquired immunodeficiency syndrome (AIDS), in which Kaposi's sarcoma occurs with mild immunodeficiency and pneumocystis carinii pneumonia occurs with more profound immunodeficiency owing to the human immunodeficiency virus. Next to pulmonary disease, cancer is the leading cause of death in A-T.

A human cell line isolated from a lung metastasis of a malignant fibrous histiocytoma was studied chromosomally. The cell line had a modal chromosome number of 59 with multiple numerical and morphologic chromosome changes and marker chromosomes. A putative clone from this cell line had a modal number of 41 with exclusively acrocentric chromosomes and was clearly not human but mouse in origin.

Chromosome studies on gallbladder adenocarcinoma in a Papago Indian woman were performed. These studies revealed a high degree of aneuploidy including multiple instances of missing chromosomes, extra chromosomes, and chromosome rearrangements. Double minute chromosomes and homogeneous staining regions on chromosomes were present in the cancer cells. To our knowledge this is the first report on the cytogenetic analysis of a gallbladder cancer. Chromosome studies on gallbladder cancers will be of unusual interest because of the relatively high frequency of this rare genetic form of cancer in American Indians.

Certain fragile sites may possibly predispose to chromosome breakage and rearrangements in meiosis. To test this hypothesis, we examined 894 breakpoints found in spontaneous abortions, stillbirths and livebirths of which 165 (18.5%) were in bands with fragile sites. Compared to an expectation of 98 (11%), there was a significant excess of breakpoints in fragile site bands (P less than 0.001). Together with data from amniocenteses, there is now evidence suggesting that certain fragile sites may be prone to fragility in meiosis.

We report herein a de novo unbalanced chromosome translocation in a fetus resulting from in vitro fertilization technology. Prenatal diagnostic analysis of an amniotic fluid revealed a 46,XX,4p+ karyotype. The origin of the extra material on the short arm of chromosome 4 could not be identified by a variety of banding techniques. However, examination of fetal parts did reveal some dysmorphic features.

Since fragile sites may conceivably predispose to chromosome breakage and rearrangements in meiosis, we examined the locations of 278 breakpoints leading to chromosome rearrangements detected in amniocenteses. Of the 278 breakpoints, 59 (21%) were observed to be in bands containing fragile sites compared to an expectation of 31 (11%), a highly significant difference (P less than 0.001). The tendency for breakpoints to be in bands with fragile sites was independent of origin of the rearrangement or class of fragile site, consistent with the concept that fragile sites predispose to heritable chromosome rearrangements.

Interstitial deletion of the short arm of chromosome 17 was detected in three unrelated patients with mental retardation and multiple congenital malformations. These patients were identified at a single centre over a six month period suggesting that del(17) (p11.2p11.2) is not a rare constitutional chromosome rearrangement. Comparison of the phenotypic features in a total of 19 patients with del(17)(p11.2p11.2) shows a consistent clinical phenotype with moderate to severe mental retardation, microbrachycelphaly, prominent forehead, broad face, flat midface, prognathism, short, broad hands, and behavioural anomalies such as self-mutilation. The sex ratio is unremarkable, parental ages are normal, and survival is usually unimpaired. Chromosome resolution of at least 500 bands appears necessary to detect this deletion.

Ataxia-telangiectasia (AT) is a primary genetic immunodeficiency disease predisposing to cancer. Approximately 40% of patients with AT develop malignancy, usually of the lymphoid system. Increased chromosome breakage in AT leads to rearrangements such as translocations and inversions. The preferred chromosome breakpoints in AT involve genes in the immune system: the immunoglobulin (Ig) gene loci in chromosome bands 2p12, 14q32, and 22q11 and the T cell receptor (TCR) gene loci in chromosome bands 7p13, 7q35, and 14q11. Identical chromosome breakpoints are observed in chromosome rearrangements in normal T cells, Burkitt's lymphoma, and adult T cell leukemia. Molecular analysis of these chromosome rearrangements reveals recombination between an oncogene and Ig or between Ig and TCR. In AT, chromosome rearrangements connect the immune system to lymphoid cancer.

The genetic history in contemporary pedigree form is a useful tool for historical reading and study. The pedigree provides a guide to related personages and a data base for analysis. These points are illustrated by the family of Levi Barent Cohen, who came to London in the 18th century. There have been comparatively few consanguineous matings in the Cohen family. The family members have played central roles in Anglo-Jewish life in their own right and through marriage to other families such as the Montefiores and Rothschilds.

Two hematologic cases with translocations involving chromosomes #3 and #12 are described. The first case is that of a myeloproliferative disorder (preleukemia?) associated with a (3;12)(q29;q24) translocation in the bone marrow cells. No evidence of leukemic transformation has appeared to date. The second case is that of acute leukemia (AL) (M4 type) in which leukemic cells with t(3;12)(p14;q24) were seen. The roles of chromosomes #3 and #12 in hematopoiesis are considered, and the abnormalities affecting these chromosomes in various hematologic disorders have been tabulated and correlated. Abnormalities in chromosomes #3 and #12 appear to be common and nonrandom in hematologic diseases of a premalignant and a malignant type.