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L S Friedman

Publications and source records attributed to L S Friedman.

At least 37 records · Page 2Linked to original sources
PubMed1997

Mutation analysis of BRCA1 and BRCA2 in a male breast cancer population.

A population-based series of 54 male breast cancer cases from Southern California were analyzed for germ-line mutations in the inherited breast/ovarian cancer genes, BRCA1 and BRCA2. Nine (17%) of the patients had a family history of breast and/or ovarian cancer in at least one first-degree relative. A further seven (13%) of the patients reported breast/ovarian cancer in at least one second-degree relative and in no first-degree relatives. No germ-line BRCA1 mutations were found. Two male breast cancer patients (4% of the total) were found to carry novel truncating mutations in the BRCA2 gene. Only one of the two male breast cancer patients carrying a BRCA2 mutation had a family history of cancer, with one case of ovarian cancer in a first-degree relative. The remaining eight cases (89%) of male breast cancer with a family history of breast/ovarian cancer in first-degree relatives remain unaccounted for by mutations in either the BRCA1 gene or the BRCA2 gene.

Aged↗
PubMed1997

A low proportion of BRCA2 mutations in Finnish breast cancer families.

One hundred breast cancer families were identified at the Helsinki University Central Hospital in Finland and were screened for germ-line mutations in the coding regions and splice boundaries of the BRCA2 gene. Eight families (8%) were found to carry five different mutations, all of which are predicted to prematurely truncate the protein product. These BRCA2 families have early-onset breast cancer (mean and median age = 49 years), with four of the eight families including ovarian cancer but with no families including male breast cancer. A wide spectrum of other cancers also is seen in these families. Three mutations were identified in more than one family, and haplotype analysis in the families suggested a common founder for each recurrent mutation. One recurrent mutation, 999del5, previously has been noted as a common mutation in Iceland. The relationship between the Icelandic 999del5 mutation and the Finnish 999del5 mutation was explored by comparison of families from both countries. A common haplotype covering a minimal region intragenic to the BRCA2 gene was shared between the Icelandic and the Finnish mutation carriers.

Adult↗
PubMed1996

Characterization of EZH1, a human homolog of Drosophila Enhancer of zeste near BRCA1.

Recent transcription mapping efforts within chromosome 17q21 have led to the identification of a human homolog of the Drosophila gene Enhancer of zeste, E(z). A member of the Polycomb group (Pc-G) of proteins, Drosophila E(z) acts as a negative regulator of the segment identity genes of the Antennapedia and Bithorax complexes. Here we report the full-length protein coding sequence of human EZH1 (Enhancer of zeste homolog 1) and compare the respective protein sequences in both species. EZH1 encodes a protein of 747 amino acids that displays 55% amino acid identity overall (70% similarity) with Drosophila E(z). The strongest homology was noted (79% identity, 89% similarity) within the carboxy-terminal 245 amino acids, including the SET domain, a region of E(z) also conserved in other Drosophila proteins with roles in development and/or chromatin structure. A large Cysrich region with a novel spatial pattern of cysteine residues was also conserved in both EZH1 and E(z). The strong sequence conservation suggest potential roles for EZH1 in human development as a transcriptional regulator and as a component of protein complexes that stably maintain heterochromatin. EZH1 is expressed as two major transcripts in all adult and fetal human tissues surveyed; comparison of cloned cDNAs suggests that alternative splicing may account for at least part of the transcript size difference. Analysis of one cDNA revealed an unusual splicing event involving EZH1 and a tandemly linked gene GPR2 and suggests a potential mechanism for modifying the EZH1 protein in the conserved C-terminal domain. The sequence and isolated cDNAs will provide useful reagents for determining the function of EZH1 and the importance of the evolutionarily conserved domains.

Adult↗
PubMed1996

Management of portal hypertension and its complications.

In the setting of chronic liver disease, portal hypertension and its complications pose major challenges in management. Once it develops, portal hypertension is the source of potentially devastating sequelae, including life-threatening hemorrhage, infection, renal failure, and encephalopathy. Improved understanding of the pathophysiology of these conditions has led to advances in endoscopic, radiologic, medical, and surgical management. The possibility in selected cases of successful amelioration of portal hypertension and its dreaded complications by liver transplantation highlights the importance of timely and careful management of patients with decompensated cirrhosis.

Ascites↗
PubMed1996

Founding BRCA1 mutations in hereditary breast and ovarian cancer in southern Sweden.

Nine different germ-line mutations in the BRCA1 breast and ovarian cancer susceptibility gene were identified in 15 of 47 kindreds from southern Sweden, by use of SSCP and heteroduplex analysis of all exons and flanking intron region and by a protein-truncation test for exon 11, followed by direct sequencing. All but one of the mutations are predicted to give rise to premature translation termination and include seven frameshift insertions or deletions, a nonsense mutation, and a splice acceptor site mutation. The remaining mutation is a missense mutation (Cys61Gly) in the zinc-binding motif. Four novel Swedish founding mutations were identified: the nucleotide 2595 deletion A was found in five families, the C 1806 T nonsense mutation in three families, the 3166 insertion TGAGA in three families, and the nucleotide 1201 deletion 11 in two families. Analysis of the intragenic polymorphism D17S855 supports common origins of the mutations. Eleven of the 15 kindreds manifesting BRCA1 mutations were breast-ovarian cancer families, several of them with a predominant ovarian cancer phenotype. The set of 32 families in which no BRCA1 alterations were detected included 1 breast-ovarian cancer kindred manifesting clear linkage to the BRCA1 region and loss of the wild-type chromosome in associated tumors. Other tumor types found in BRCA1 mutation/haplotype carriers included prostatic, pancreas, skin, and lung cancer, a malignant melanoma, an oligodendroglioma, and a carcinosarcoma. In all, 12 of 16 kindreds manifesting BRCA1 mutation or linkage contained ovarian cancer, as compared with only 6 of the remaining 31 families (P<.001). The present study confirms the involvement of BRCA1 in disease predisposition for a subset of hereditary breast cancer families often characterized by ovarian cancers.

Adult↗
PubMed1995

Mutation analysis of the BRCA1 gene in ovarian cancers.

Germline mutations of the BRCA1 tumor suppressor gene on chromosome 17q are involved in a significant fraction of hereditary breast and ovarian cancers. Allelic deletions that include the BRCA1 locus are common in breast and ovarian cancers, implying that somatic mutations of this gene may play an important role in the more common sporadic forms of these tumors as well. The recent cloning of BRCA1 allows direct testing of this hypothesis. A combination of single strand conformation and sequencing analyses was used to examine the 22 coding exons and intronic splice donor and acceptor regions of BRCA1 for mutations in 115 unselected cases of epithelial ovarian carcinoma. Seven mutations were identified, all of which were present in the germlines of patients with remarkable family or medical histories of breast and/or ovarian cancer. Eighty-nine of these tumors were examined for loss of heterozygosity in the BRCA1 region of chromosome 17q, and 67% of the tumors studied exhibited allelic deletions that included this region. These data are consistent with the hypothesis that BRCA1 mutations are involved in the etiology of hereditary ovarian carcinomas but occur rarely in sporadic tumors, and that the frequent allelic loss on chromosome 17q in this cancer type reflects the involvement of an additional tumor suppressor gene(s).

Adult↗
PubMed1995

22 genes from chromosome 17q21: cloning, sequencing, and characterization of mutations in breast cancer families and tumors.

In our effort to identify BRCA1, 22 genes were cloned from a 1-Mb region of chromosome 17q21 defined by meiotic recombinants in families with inherited breast and/or ovarian cancer. Subsequent discovery of another meiotic recombinant narrowed the region to approximately 650 kb. Genes were cloned from fibroblast and ovarian cDNA libraries by direct screening with YACs and cosmids. The more than 400 cDNA clones so identified were mapped to cosmids, YACs, and P1 clones and to a chromosome 17 somatic panel informative for the BRCA1 region. Clones that mapped back to the region were hybridized to each other and consolidated into clusters reflecting 22 genes. Ten genes were known human genes, 5 were human homologs of known genes, and 7 were novel. Each gene was sequenced, compared to genes in the databases to find homologies, and analyzed for mutations in BRCA1-linked families and tumors. Eight mutations were found in tumors or families and not in controls. In the gene encoding alpha-N-acetylglucosaminidase, approximately 100 kb proximal to the 650-kb linked region, somatic nonsense, missense, and splice junction mutations occurred in 3 breast tumors, but not in these patients' germline DNA nor in controls. In an ets-related oncogene in the linked region, a missense mutation cosegregated with breast cancer in one family and was not observed in controls. In a human homolog of a yeast pre-mRNA splicing factor, 3 different mutations cosegregated with breast cancer in 3 families and were not observed in controls. In these and the other genes in the region, 36 polymorphic variants were observed in both cases and controls.

BRCA1 Protein↗
PubMed1995

Alcohol withdrawal: a nationwide survey of inpatient treatment practices.

OBJECTIVE: To describe current practices employed in the inpatient treatment for alcohol withdrawal. DESIGN: Survey. SETTING: Inpatient alcoholism treatment programs in the United States. PARTICIPANTS: Medical directors of 176 (69%) of 257 eligible programs randomly selected from a national listing. RESULTS: The medical directors estimated that of all inpatients treated for alcohol withdrawal at the programs, 68% received one of the following medications. Benzodiazepines, including the long-acting chlordiazepoxide (33%) and diazepam (16%), and less frequently the short-acting oxazepam (7%) and lorazepam (4%), were the most commonly used agents. Barbiturates (11%), phenytoin (10%), clonidine (7%), beta-blockers (3%), carbamazepine (1%), and antipsychotics (1%) were less frequently given. Drug was most often given on a fixed dosing schedule with additional medication "as needed" (52% of the programs). Only 31% of the programs routinely used a standardized withdrawal severity scale to monitor patients. Mean duration of sedative treatment was three days; inpatient treatment, four days. Use of fixed-schedule regimens was associated with longer sedative treatment (mean four vs three days, p < 0.01). Northeast census region location and psychiatrist program director were significantly associated with longer sedative and inpatient treatment duration. CONCLUSIONS: The most commonly reported regimen for alcohol withdrawal included three days of long-acting benzodiazepines on a fixed schedule with additional medication "as needed." Standardized monitoring of the severity of withdrawal was not common practice. The directors reported using a variety of other regimens, some not known to prevent the major complications of withdrawal. Although geographic location and director specialty were significantly associated with treatment duration, much of the variation in treatment for alcohol withdrawal remains unexplained.

Adrenergic beta-Antagonists↗
PubMed1995

Irritable bowel syndrome. Managing the patient with abdominal pain and altered bowel habits.

Irritable bowel syndrome is a common complex of syndromes thought to be generated by a motility or sensory disturbance of the gastrointestinal tract. It is a frequent cause of chronic abdominal pain and altered bowel habits. Patients who seek medical attention for irritable bowel syndrome often do so because of psychosocial factors. Therapy remains largely empirical, directed toward the relief of symptoms in the context of a supportive physician-patient relationship.

Ambulatory Care↗
PubMed1995

Chronic viral hepatitis and the management of chronic renal failure.

Effective control measures to reduce the spread of HBV in dialysis units have had a major beneficial impact on the management of patients with chronic renal failure (Table 3). The exact impact of chronic HBV infection on graft and patient survival following RT remains unclear, and the outcome may depend in great part on the severity of the pre-RT liver disease. RT should only be offered to HBV-infected patients after careful consideration of all the pertinent data, including results of liver biopsy. Advances in HBV vaccination may further decrease the risk of infection in patients on HD. Our understanding of HCV is evolving rapidly, but the question of the risk of transmission of HCV within dialysis units is still unsettled and thus recommendations about isolation of HCV-infected patients are not possible. Although RT does not appear to be deleterious in many HCV-infected patients, histologic and clinical evidence of severe liver disease should also prompt caution in offering RT. Longer term studies are required to assess the ultimate effect of RT in patients with HCV. Clearly, subjective improvement of quality of life associated with successful RT compared to chronic dialysis should not be withheld lightly. Pending further experience, use of organs from anti-HCV-positive donors in non-emergent situations is best avoided. The role of antiviral agents in RT recipients with chronic viral hepatitis also remains to be defined. Improved supportive care of patients with chronic renal disease, including erythropoietin therapy, as well as improved tests for anti-HCV screening of donor blood will help to further diminish exposure to HCV in HD units.

Chronic Disease↗
PubMed1995

Adolescents' preferences regarding human immunodeficiency virus (HIV)-related physician counseling and HIV testing.

OBJECTIVE: To assess adolescents' preferences regarding human immunodeficiency virus (HIV)-related physician counseling and HIV testing. DESIGN: Anonymous, self-report survey. SETTING: Metropolitan Boston public schools. PARTICIPANTS: Students in 9th and 12th grade from 10 schools. RESULTS: Of the 845 students (99%) who completed the survey, 53% were female, 50% seniors, and 76% white. Although 86% had regular physicians, only 27% reported ever discussing HIV with a physician. The majority wanted a physician to give them information about sexually transmitted diseases (82%), condoms (73%), sex (70%), safe sex (80%), and HIV (85%). Most wanted physicians to ask about personal experiences with sexually transmitted diseases (64%), condoms (59%), safe sex (67%), and HIV (72%). Seniors, students with female physicians, and students who had previously discussed sex with physicians were significantly more likely to want physicians to ask personal questions about HIV-related risk behaviors. Most, however, felt uncomfortable initiating a discussion about safe sex (59%), condoms (67%), sex (69%), and homosexuality (78%). More students preferred to speak with physicians (36%) than with family members (16%) or teachers (2%) about their personal risk of acquiring HIV, although 32% preferred to speak with friends. More preferred to be tested for HIV by someone who did not know them (40%) than by someone who did (32%). When asked about specific testing sites, 25% preferred a place that does only HIV testing, and 22% preferred their regular physicians' offices. CONCLUSIONS: Adolescents want physicians to give them information and to ask personal questions about HIV and HIV-related risk behaviors, and they prefer that the physicians initiate the discussion. Although they have no clear preference for testing sites, many teenagers prefer to be tested by someone who does not know them.

Adolescent↗