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Biomedical subjects

G B Mann

Publications and source records attributed to G B Mann.

28 records · Page 2Linked to original sources
PubMed1995

A mutation in the epidermal growth factor receptor in waved-2 mice has a profound effect on receptor biochemistry that results in impaired lactation.

The mutant mouse waved-2 (wa-2) is strikingly similar to transforming growth factor alpha-deficient mice generated by gene targeting in embryonic stem cells. We confirm that wa-2 is a point mutation (T-->G resulting in a valine-->glycine substitution at residue 743) in the gene encoding the epidermal growth factor (EGF) receptor. wa-2 fibroblastic cells lack high-affinity binding sites for EGF, and the rate of internalization of EGF is retarded. Although the tyrosine kinase activity of wa-2 EGF receptors is significantly impaired, NIH 3T3 cells lacking endogenous EGF receptors but overexpressing recombinant wa-2 EGF receptor cDNA are mitogenically responsive to EGF. While young and adult wa-2 mice are healthy and fertile, 35% of wa-2 mice born of homozygous wa-2 mothers die of malnutrition because of impaired maternal lactation.

3T3 Cells↗
PubMed1994

Laparoscopic creation of pericardial window.

Malignant pericardial effusions are frequently symptomatic and usually recur after aspiration. Surgical options include pericardiectomy and transthoracic or subxiphoid pericardial window formation and, more recently, thoracoscopic pericardial window formation. The authors report their first four cases of laparoscopic creation of pericardial windows. The treatment has been effective and minimally traumatic.

Aged↗
PubMed1994

Insights into the physiology of TGF alpha and signaling through the EGF receptor revealed by gene targeting and acts of nature.

Transforming growth factor alpha (TGF alpha) is one of a group of structurally-related growth factors (the epidermal growth factor family of ligands) that interact with one or other members of the epidermal growth factor family of protein tyrosine kinase receptors (EGF-R's). A number of excellent reviews detailing our knowledge of this area have been recently published (Carpenter and Wahl, 1991; Derynck, 1992; Prigent and Lemoine, 1992). Rather than add to their number, this review focuses on new insights into the importance of TGF alpha and signaling through the EGF receptor considered in the context of the laboratory mouse. The new information has emerged from analysis of mutant mice generated either by classical gene targeting in embryonic stem (ES) cells or by accidents of nature. In addition to their intrinsic interest, these mice are proving invaluable in determining the importance of EGF receptor signaling in wound healing and as a contributing factor in the conversion of a normal cell into its tumorigenic counterpart.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Mice with a null mutation of the TGF alpha gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation.

Mice homozygous for a disrupted transforming growth factor alpha (TGF alpha) gene are healthy and fertile, although some older mice show evidence of corneal inflammation. In contrast with TGF alpha +/- and +/+ animals, TGF alpha -/- mice have a pronounced waviness of the coat. Histological examination of the skin from TGF alpha -/- mice reveals a dramatic derangement of hair follicles. Mice with a disrupted TGF alpha gene also have curly whiskers, first evident on the day of birth. The phenotype of TGF alpha -/- mice is remarkably similar to that of the mouse mutant waved-1 (wa-1). Offspring resulting from crosses between TGF alpha -/- and wa-1 mice display the curly whisker-coat phenotype, indicating that the basis of the wa-1 phenotype is a mutation in the TGF alpha gene. These observations suggest that TGF alpha plays a pivotal role in determining skin architecture and in regulating hair development.

Animals↗
PubMed1993

Linkage of the murine transforming growth factor alpha gene with Igk, Ly-2, and Fabp1 on chromosome 6.

TGF alpha is a mitogenic polypeptide found in the conditioned media of transformed cell lines as well as in various solid tumors. Although its physiological role in normal tissues is uncertain, the autocrine action of TGF alpha on the EGF receptor is postulated to play a role in tumorigenesis. To explore the possibility that pre-existing mouse mutants might have concordance with the mouse TGF alpha locus (Tgfa) we sought to establish the chromosomal localization of the murine TGF alpha gene. Using Southern analysis we have detected NcoI and PvuII RFLPs in the TGF alpha gene of progenitor RI mouse strains. These RFLPs have been used to analyze four different RI sets of DNA and to assign Tgfa to the 35-cM region of chromosome 6. Linkage has been established and the data suggest that the distance between Igk and wa-1 anchor loci may be less than 8 cM and that the gene order for the proximal to mid region of mouse chromosome 6 may be: Ggc-Xmmv27-[Brp-1, Lvp-1, Ms6-4]-[Igk, Ly2, Ly3 Odc-rs5, Rn7s-6, Fabp1]-[Tgfa/wa-1]-IL5-R. Homology of synteny has been further defined between the proximal region of mouse chromosome 6 and with the 2p13-p11 region of human chromosome 2 encompassing TGFA, IGK, CD8A, and FABP1.

Animals↗
PubMed1993

Identification of germ-line chimaeras by polymerase chain reaction and isoenzyme analysis of mouse spermatozoa.

In this study a rapid, simple and inexpensive procedure is described which allows potential germ-line male mice to be identified with confidence. Spermatozoa recovered by uterine washing following mating with normal female mice was analysed in two ways. First, the patterns of expression of the different isoforms of glucose phosphate isomerase were determined. Since the glucose phosphate isomerase isoforms expressed in embryo stem (ES) cell lines are frequently different from those associated with the host blastocyst, it is possible to determine the proportion of spermatozoa produced by an individual animal that was of ES cell or host-blastocyst origin. Second, DNA of spermatozoa was subjected to polymerase chain reaction (PCR) analysis using primers with specificity for the targeted mutation in the ES cells. The PCR analysis was particularly valuable in identifying germ cell chimaeras in which the contribution of ES-derived spermatozoa was significantly less than that specified by the host blastocyst.

Animals↗
PubMed1987

Accounting guidelines developed for malpractice claims.

Recently, the AICPA developed a Statement of Position on medical malpractice claims of healthcare providers. The statement was developed to provide guidance and consistency for accounting and reporting practices for healthcare providers. The proper application of the Statement of Position requires a thorough understanding of the provider's claim and incident identification procedures. And this understanding becomes more critical as providers begin to realize the restrictive opportunities of conventional malpractice insurance coverage.

Accounting↗
PubMed1985

A comparative study of PALA, PALA plus 5-FU, and 5-FU in advanced breast cancer.

Sixty-three patients with Stage IV breast carcinoma refractory to standard combination chemotherapy agents such as 5-fluorouracil (5-FU) were entered into a study to determine the efficacy of a multiple dose schedule of N-(phosphonacetyl)-L-aspartic acid (PALA) and whether the addition of PALA improves the therapeutic efficacy of 5-FU. Patients were randomized to receive either PALA, 800 to 1000 mg/m2 per day for 5 days every 2 weeks; or PALA + 5-FU, 400 mg/m2 per day for 5 days, and 300 mg/m2 per day for 5 days every 28 days, respectively. The PALA alone arm of the study was closed after 20 patients had been treated and was replaced by 5-FU, 300 to 400 mg/m2 per day for 5 days every 21 days. Overall response rates were 5% for PALA alone, 28% for PALA + 5-FU, and 14% for 5-FU alone. All patients who responded to PALA + 5-FU or 5-FU alone had received prior therapy in which 5-FU was part of the combination chemotherapy program and were considered refractory to this drug. Toxicity affected the gastrointestinal tract but was tolerable in all three arms of the study. Myelosuppression was negligible for PALA and PALA + 5-FU and moderate for 5-FU. The authors concluded that PALA + 5-FU was superior to PALA alone in the therapy of these heavily pretreated patients. PALA alone had marginal efficacy. In view of its low hematologic toxicity, PALA + 5-FU may be combined with more myelosuppressive drugs. Additional studies are necessary to ascertain whether PALA + 5-FU is therapeutically superior to a full-dose schedule of 5-FU.

Adult↗
PubMedDate not supplied

Does the extent of operation influence the prognosis in patients with melanoma metastatic to inguinal nodes?

BACKGROUND: The role of pelvic lymphadenectomy in melanoma metastatic to the superficial inguinal region remains controversial. Some researchers advocate aggressive surgical management, whereas others feel that outcome depends more on extent of disease rather than extent of treatment. We reviewed our recent experience to investigate possible therapeutic effects of extended surgery. METHODS: We performed a retrospective clinical and pathological review of 227 consecutive patients having superficial (SLND) or combined inguinal lymphadenectomy (CLND) for cutaneous melanoma. RESULTS: A total of 174 SLNDs and 53 CLNDs were performed. Overall 5-year survival for node-positive patients was 39%. Survival for patients with positive superficial nodes was 40%; for those with positive deep nodes it was 35% (P = ns). In node-positive patients, number and size of involved lymph nodes and the presence of extranodal spread, failure to receive adjuvant therapy, and tumor ulceration were associated with poorer prognosis. Extent of surgery was not associated with differential survival, although CLND patients had worse pathological features. Subgroup analysis showed no significant survival difference between SLND and CLND. CONCLUSIONS: Some patients with deep nodal involvement apparently are cured by CLND. However, it is the biology of the disease and not the extent of surgery that primarily governs outcome. Patients with clinical or radiological evidence of pelvic nodal disease without evidence of systemic disease should have a CLND, but we find no evidence to support CLND if the pelvic nodes are clinically and radiologically negative.

Adolescent↗