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Biomedical subjects

J Spicer

Publications and source records attributed to J Spicer.

At least 19 recordsLinked to original sources

LIP1, a cytoplasmic protein functionally linked to the Peutz-Jeghers syndrome kinase LKB1.

LKB1 is a serine/threonine kinase which is inactivated by mutation in the Peutz-Jeghers polyposis and cancer predisposition syndrome (PJS). We have identified a novel leucine-rich repeat containing protein, LIP1, that interacts with LKB1. The LIP1 gene consists of 25 exons, maps to human chromosome 2q36 and encodes a protein of 121 kDa. LIP1 appears to be a cytoplasmically located protein whereas we and others have shown previously that LKB1 is predominantly nuclear, with only a small proportion of cells showing strong cytoplasmic expression. However, when LKB1 and LIP1 are co-expressed, the proportion of cytoplasmic LKB1 dramatically increases, suggesting that LIP1 may regulate LKB1 function by controlling its subcellular localization. Ectopic expression of both LKB1 and LIP1 in Xenopus embryos induces a secondary body axis, providing further evidence for a functional link between the two proteins. This phenotype resembles the effects of ectopic expression of TGFbeta superfamily members and their downstream effectors. A possible role for LIP1 and LKB1 in TGFbeta signalling is supported by the observation that LIP1 interacts with the TGFbeta-regulated transcription factor SMAD4, forming a LKB1-LIP1-SMAD4 ternary complex. SMAD4 mutations give rise to juvenile polyposis syndrome, which is clinically similar to PJS. Our data suggest an unsuspected mechanistic link between these two syndromes.

AMP-Activated Protein Kinase Kinases↗

Professional lability insurance: I. A historical perspective.

Medical professional liability insurance (also known as malpractice insurance) is designed specifically to protect physicians, clinics, hospitals and health care facilities, and other health personnel in the event that a patient files a claim against them, alleging negligence, with resulting injury or harm. It is one of the largest expenses for any medical practice and is a high priority concern of every physician. The market for this insurance, the approach to evaluating it, and the cost of it have changed dramatically in the last 20 years.

History, 20th Century↗

Theoretical perspectives on suicide in gay men with AIDS.

Suicide among gay men with AIDS constitutes a significant theoretical and practical problem. In order to understand this problem it is necessary to consider the specific circumstances that surround these individuals. Whilst there are many theories of suicide with which to address the problem, few are able to capture the special context within which gay men with AIDS live. This article explores three broad concepts from the theoretical literature on suicide that have explanatory potential in this unique context. The three concepts are: the search for meaning in the midst of suffering, Shneidman's [Shneidman, E., 1985. Definition of Suicide. John Wiley, New York] notion of unendurable psychological pain, and hopelessness. This article attempts to demonstrate how these three concepts can incorporate the experiences of gay men with AIDS and contribute to understanding the problem of suicide in this population.

Acquired Immunodeficiency Syndrome↗

The mouse Peutz-Jeghers syndrome gene Lkb1 encodes a nuclear protein kinase.

The protein kinase gene LKB1 has recently been identified as the gene mutated in the Peutz-Jeghers cancer predisposition syndrome. This condition is characterized by inherited susceptibility to a range of cancers but in particular those of the gastrointestinal tract. Here we have characterized the mouse Lkb1 gene. The mouse Lkb1 gene consists of 10 exons covering approximately 15 kb in length, maps to mouse chromosome 10 and encodes a protein showing strong sequence similarity to human LKB1. The 3" end of Lkb1 in the mouse is in very close proximity to the 3" end of an apparently unrelated gene R29144/1 and it seems probable that overlapping transcripts of the two genes are produced. Using transfection of Lkb1 cDNAs we have shown that Lkb1 is most likely a nuclear protein and have defined a nuclear localization signal within the protein sequence. Thus the defect in Peutz-Jeghers syndrome may directly result in changes in gene expression in the nucleus of target cells.

AMP-Activated Protein Kinases↗

A new measure of conversational experience: the speaking extent and comfort scale (SPEACS).

Few measures exist which directly assess aspects of conversational experience. We present and provide a psychometric assessment of the Speaking Extent and Comfort Scale (SPEACS), a new 20-item measure which assesses four aspects of past conversational experience: the extent and comfort of both general conversations and in conversations specifically about the self. All four SPEACS subscales exhibited good test-retest reliability. As predicted, the subscales related positively to social competence, disclosure, assertiveness, and perceived availability of someone to talk to, and negatively to social avoidance and social anxiety, providing support for their construct validity. Internal consistency data demonstrated that people tend to vary in how often and how comfortable they feel having conversations with different people. SPEACS offers a range of potential applications in areas with a focus on social networks, social experience and interaction, and the possibility of extension to other dimensions of conversational experience.

Adolescent↗

Development of a radiopharmaceutical information database.

OBJECTIVE: This article describes the development of a radiopharmaceutical (RP) computer database. Development and implementation of the database and services provided are presented. METHODS: A commercial database program was used to develop the structure for a radiopharmaceutical information database (RID) and to classify interaction information into several categories. The database is accessible to a variety of users through a network server. RESULTS: Information entered into the RID may be accessed easily and rapidly. The RID provides a wide spectrum of information services to its customers. CONCLUSION: The RID described is the first attempt to develop a database capable of entry and retrieval of RP information in an efficient and timely manner. The database is easy to use and maintain, and has virtually unlimited storage space on a network drive.

Database Management Systems↗

Treatment of patients with transitional-cell carcinoma of the urothelial tract with ifosfamide, paclitaxel, and cisplatin: a phase II trial.

PURPOSE: A phase II trial of ifosfamide, paclitaxel, and cisplatin (ITP) was conducted in previously untreated patients with advanced transitional-cell carcinoma (TCC) to assess its efficacy and toxicity. PATIENTS AND METHODS: Thirty patients with metastatic or unresectable TCC were treated with ifosfamide 1.5 g/m2/d for 3 days with paclitaxel 200 mg/m2 over 3 hours and cisplatin 70 mg/m2 on day 1 of each 28-day treatment cycle. Therapy was continued for a maximum of six cycles. Prophylactic hematopoietic growth factor (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was given on days 6 to 17 of each cycle. RESULTS: Twenty-three of 29 assessable patients (79%; 95% confidence interval [CI], 60% to 92%) demonstrated a major response (six complete [CR] and 17 partial [PR]) with response durations that ranged from 5 to 24+ months. Five patients with T4 bladder primary tumors had a major response, two with pathologic CR. At a median follow-up duration of 17.9 months, nine (31%) patients remain disease-free (range, 10+ to 24+). Hematologic toxicity included anemia, thrombocytopenia, and neutropenia; febrile neutropenia was observed in 17% of patients and 4% of cycles. No grade 4 nonhematologic toxicity was observed. Grade 3 nonhematologic toxicity included alopecia, allergy (3%), renal insufficiency (13%), and neuropathy (10%). Dose reductions or drug omissions were necessary for adverse events in seven (23%) patients. CONCLUSION: ITP is an active, well-tolerated regimen in previously untreated patients with TCC of the urothelial tract. Further study of this regimen in patients with both TCC and non-transitional-cell urothelial tumors is ongoing.

Adult↗

Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin.

PURPOSE: To assess the durability of response and overall survival for patients with good-risk metastatic germ cell tumors (GCT) treated with four cycles of etoposide and cisplatin (EP). PATIENTS AND METHODS: Two hundred fourteen patients treated with EP on two consecutive randomized trials for good-risk metastatic GCT were the subject of this retrospective study. The response to therapy, relapse and survival status, and results of salvage therapy are reported. RESULTS: One hundred ninety-five patients (91%) achieved a complete response (CR). This included 182 patients (85%) who achieved a CR to chemotherapy alone and 13 patients (6%) who achieved a CR to chemotherapy plus surgical resection of viable GCT. Seventeen patients (9%) have relapsed from CR. The median time to relapse was 10 months, and the longest duration from treatment to relapse was 36 months in a patient who received three of four planned courses of therapy. Eight patients who either achieved an incomplete response (IR) or relapsed were rendered continuously disease-free by salvage therapy and are alive. One hundred eighty-three patients (86%) are alive at a median follow-up of 7.6 years. CONCLUSION: Four cycles of EP constitute effective therapy and can be offered to patients with good-risk GCT. In patients with intermediate- and poor-risk GCT, clinical trials remain a priority to identify more effective treatment.

Adolescent↗