Structure, chromosomal localisation and expression of the murine dominant negative helix-loop-helix Id4 gene.

Id proteins antagonise the functional properties of DNA-binding, basic helix-loop-helix transcription factors. Id proteins inhibited cell differentiation in various model systems, both in vitro and in vivo. They are transcriptionally and post-transcriptionally regulated during cell cycle progression and promote cell proliferation. In order to establish the molecular and functional properties of Id4, we analysed structure, chromosomal localisation and expression of the murine Id4 gene. Sequence analysis indicated that the Id4 gene consists of three exons. Multiple transcription start sites map about 300 bp upstream of the ATG translational start codon within a 30-bp region of the Id4 promoter, which lacks a classic TATA box. Expression of the Id4 gene results in four major transcripts, most likely generated by differential use of polyadenylation sites. Abundance of the four transcripts varies across tissues, suggesting tissue-specific regulation of polyadenylation and/or post-transcriptional regulation of Id4 expression. However, the Id4 gene seems to be expressed as a single protein. Id4 expression is switched on during embryogenesis between day 7.5 and 9.5 of gestation and is most abundant in adult brain, kidney and testis. Id4 maps to chromosome 13 of the mouse.

Lessons for the health care industry from America's experience with public utilities.

In the United States, the traditional public utilities, power and telecommunications, along with health care, are being deregulated and becoming increasingly competitive, especially on price. Regulation of the public utilities has occurred for the past century not simply because they have been monopolies, but, more importantly, because they are "industries affected with the public interest," that is industries which: 1. provide an essential service, 2. benefit from public prequisites, and 3. would cause great public harm if mismanaged. Consequently, the presence of competition in these industries does not negate the need for regulation. Regulation of these industries is best understood as being along the three sides of a "triangle of public interests"--quality, public accountability, and universal service. Examples are provided of these types of regulation in power and telecommunications, even in current "deregulatory" legislation. Health care reform activists in the United States have lately paid attention mostly to the first two legs of the triangle; they are encouraged to focus creatively on the third leg--universal health care.

Preoperative irradiation for head and neck cancer: results of a prospective study.

Two hundred forty-eight patients with primary epidermoid carcinoma of the oral cavity, oropharynx, and hypopharynx, stages II, III, and IV were entered into a prospective randomized clinical trial of preoperative irradiation therapy (700 rads X 2) and surgery versus surgery alone. At 5 years both groups had a similar survival when analyzed according to stage of disease, primary site, or lymph node status. However, the group of patients receiving preoperative irradiation showed a lower incidence of local recurrence (22% versus 36%) preoperative irradiation showed a lower incidence of local recurrence (22% versus 36%) (P = 0.02). From this study we conclude that preoperative irradiation in this dose schedule has little influence on the ultimate outcome after surgical treatment of head and neck cancer.

Radiation therapy for esophageal cancer: the Medical College of Virginia experience.

In a retrospective review of 70 patients with carcinoma of the esophagus treated by external beam irradiation therapy from 1968 to 1977 at the Medical College of Virginia, we correlated survival with race, age, sex, histology, and site of tumor. Results of treatment were also analyzed in relation to the length of the esophagus treated, the total area of the treatment field, and the total tumor dose. From this analysis it appears that radiotherapy has a place in the palliative treatment of esophageal cancer and that palliation is independent of the total volume and dose. There is indication that with higher dosage the survival rate is slightly higher.

Preoperative radiotherapy for stage III carcinoma of the breast.

We have concluded from these observations in this pilot study that preoperative radiation therapy does not play a particularly helpful role in the management of patients who have the clinical finding of borderline operable carcinoma of the breast and it does not improve the survival rate. Patients within this category of locally advanced disease must be considered to have systemic metastatic disease at the time of diagnosis, as has previously been stressed by many. For this reason, any therapy directed to the regional area for local control must be combined with some form of systemic therapy if there is to be any hope for an increase in survival time.