Lowered amounts of the tissue-specific transcription factor LFB1 (HNF1) correlate with decreased levels of glutathione S-transferase alpha messenger RNA in human renal cell carcinoma.

Human renal cell carcinoma is characterized by the loss of differentiation markers such as glutathione S-transferase alpha (GST-alpha). In this paper we show that the promoter of a GST-alpha gene contains a functional binding site for the cell-specific transcription factor LFB1 (HNF1). To investigate the potential role of LFB1 in the down-regulation of GST-alpha expression, we have compared the amount and the binding activity of the LFB1 protein between normal kidney and tumor tissue. By Western analysis and gel retardation assay using a monoclonal antibody specific for LFB1 we show that in 11 of 14 carcinomas the amount of LFB1 is clearly reduced compared to the corresponding normal tissue and that in all 14 renal carcinomas LFB1 binding activity is diminished. As in the same samples the abundance of GST-alpha mRNA is lower than in the normal tissue, we postulate that the loss of LFB1 binding activity might be responsible for the decreased expression of the GST-alpha gene in renal cell carcinoma.

Leptin is inversely related to age at menarche in human females.

Over the last century there has been a trend toward an earlier onset of menarche attributed to better nutrition and body fatness. With the discovery of the obesity gene and its product, leptin, we reexamined this hypothesis from a new perspective. As delayed menarche and leanness are considered risk factors for osteoporosis, we also evaluated the relation between leptin and bone mass. Body composition and serum leptin levels were measured, and the timing of menarche was recorded in 343 pubertal females over 4 yr. Body composition was measured by dual x-ray absorptiometry, and leptin by a new RIA. All participants were premenarcheal at baseline (aged 8.3-13.1 yr). Leptin was strongly associated with body fat (r = 0.81; P < 0.0001) and change in body fat (r = 0.58; P < 0.0001). The rise in serum leptin concentration up to the level of 12.2 ng/mL (95% confidence interval, 7.2-16.7) was associated with the decline in age at menarche. An increase of 1 ng/mL in serum leptin lowered the age at menarche by 1 month. A serum leptin level of 12.2 ng/mL corresponded to a relative percent body fat of 29.7%, a body mass index of 22.3, and-body fat of 16.0 kg. A gain in body fat of 1 kg lowered the timing of menarche by 13 days. Leptin was positively related to bone area (r = 0.307; P < 0.0001) and change in bone area (r = 0.274; P < 0.0001). A critical blood leptin level is necessary to trigger reproductive ability in women, suggesting a threshold effect. Leptin is a mediator between adipose tissue and the gonads. Leptin may also mediate the effect of obesity on bone mass by influencing the periosteal envelope. This may have implications for the development of osteoporosis and osteoarthritis.

Gain in body fat is inversely related to the nocturnal rise in serum leptin level in young females.

Both genetic and environmental factors contribute to adolescent obesity. Evidence of a genetic basis for obesity development is substantial, although the exact mechanism of action has yet to be identified. The purpose of this study was to document the circadian rhythmicity of the serum leptin level in young females and to assess the impact of the change in body fat stores during growth on the nocturnal rise in the serum leptin level with implications for obesity traits. There was a significant rise in serum leptin at midnight and 0400 h, suggesting a diurnal variation in serum leptin concentrations (ANOVA F ratio = 6.2; P < 0.0001). There was also a strong association between relative total body fat and the average daytime serum leptin level (r = 0.78; P < 0.0001). The percent increase in the nocturnal leptin concentration was inversely related to the percent gain in total body fat (r = 0.45; P < 0.024). Forward stepwise regression analysis selected the change in total body fat over a 6-month interval as the most powerful determinant of the percent increase in the nocturnal leptin concentration (partial R2 = 0.203; beta = -0.450; SE of beta = 0.186; t = -2.418; P < 0.024). If the lack of a nocturnal rise in serum leptin persists over a longer period of time, it may have implications for the development of obesity, presumably by inadequate suppression of nighttime appetite.

Evidence for a posttranscriptional effect of retinoic acid on connexin43 gene expression via the 3'-untranslated region.

All-trans retinoic acid (10(-7) M) induces cell-cell communication and the expression of the gap junction protein connexin43 in mouse F9 teratocarcinoma cells. Previous experiments revealed an increase of mRNA but no change in the transcription of connexin43, suggesting a posttranscriptional mechanism responsible for the regulation of connexin43 gene expression. In transient transfection experiments using an expression vector containing the 3'-untranslated region of the connexin43 gene downstream of the luciferase coding sequence driven by the connexin43 promoter we show here that retinoic acid enhances luciferase activity via the connexin43 3'-untranslated region due to altered stability of the mRNA. Thus, retinoic acid is able to influence connexin43 gene expression at the level of mRNA stability via elements located in the 3'-untranslated region.

Analysis of connexin43 gene expression induced by retinoic acid in F9 teratocarcinoma cells.

All-trans retinoic acid (10(-7) M) induces cell-cell communication and expression of the gap junction protein connexin43 in mouse F9 teratocarcinoma cells. Northern blot analysis revealed an increase of connexin43 mRNA after treatment with retinoic acid, accompanied by an increase of the mRNA of collagen IV, a differentiation marker. To address the question at what level gene expression is enhanced by retinoic acid, nuclear run-on experiments were carried out. There was no detectable change in the level of newly transcribed connexin43 mRNA. Therefore, we postulate a post-transcriptional mechanism responsible for the regulation of connexin43 mRNA levels by retinoic acid.

Iron status, menarche, and calcium supplementation in adolescent girls.

The effects of growth, menstrual status, and calcium supplementation on iron status were studied over 4 y in 354 girls in pubertal stage 2 who were premenarcheal at baseline (x+/-SD age: 10.8+/-0.8 y). Girls were randomly assigned to placebo or treatment with 1000 mg Ca/d as calcium citrate malate. Anthropometric characteristics, bone mass, and nutritional status were measured biannually; ferritin was measured annually; and red blood cell indexes were determined at 4 y. The simultaneous effects of iron intake and menstrual status on serum ferritin, after change in lean body mass (LBM) was controlled for, were evaluated in subjects in the upper and lower quartiles of cumulative iron intake. The average maximal accumulation of LBM (386 g/mo; 95% CI: 372, 399) occurred 0.5 y before the onset of menarche. Change in LBM was a significant predictor of serum ferritin (P < 0.0001), with a negative influence on iron status (t ratio=-4.12). The 2 fitted mathematical models representing ferritin concentrations of subjects in the upper and lower quartiles of cumulative iron intake were significantly different (P < 0.018). The regression line of the ferritin concentration in menstruating girls with high iron intakes had a less negative slope than the line fit to serum ferritin concentrations in girls with low iron intakes (NS). Serum ferritin concentrations at 0, 1, 2, 3, and 4 y were not significantly different between groups. In addition, there was no significant difference between groups in any of the red blood cell indexes. In summary, growth spurt and menstrual status had adverse effects on iron stores in adolescent girls with low iron intakes (<9 mg/d), whereas long-term supplementation with calcium (total intake: approximately 1500 mg/d) did not affect iron status.

The incidence of occult metastases for cancer of the oral tongue and floor of the mouth: treatment rationale.

One hundred thirty-six surgical cases of squamous cell carcinoma of the oral tongue and floor of the mouth at the Emory University Hospitals were reviewed for the incidence of occult metastases. Thirty-five percent of the T1 T2 lesions of the anterior tongue had occult metastases. The figure was 31.5% for similarly staged lesions of the floor of the mouth. The presence of regional metastases resulted in a 2-year determinate survival rate of 37% and 32% for patients with oral tongue and floor of the mouth lesions, respectively. The poor prognosis in the study for delayed cervical metastases and the high incidence of occult cervical metastases have led the authors to propose a more aggressive therapy for the clinically negative necks in these two sites of squamous cell carcinoma of the oral cavity.

The pseudocapsule of pleomorphic adenomas (benign mixed tumors): the argument against enucleation.

The "well encapsulated" pleomorphic adenoma has at best a pseudocapsule which allows for bits of satellite tumor to be left behind at ""enucleation" surgery as well as for easy "spillage" of tumor by the overconfident surgeon. Recurrent pleomorphic adenomas then become difficult tumors to eradicate and place vital structures, such as the facial nerve, in jeopardy.

"Practical suggestions in facial plastic surgery--how i do it." "Threading" augmentation for facial wrinkles.

For hundreds of years various types of sutures and threads have been placed in the human body by surgeons. The technique of thread augmentation involves the use of colorless absorbable (Vicryl) and non-absorbable (Neurolon) suture material on a long, straight Keith needle tunneled subdermally beneath prominent facial wrinkles in an effort to make the deep grooves less severe and to augment atrophic areas about the lips and oral commissures. This may be done as an isolated procedure or as an ancillary procedure at the time of a blepharoplasty or cervicofacial rhytidectomy.

Glomus intravagale.

Glomus intravagale (paraganglioma of the nodose ganglion and/or vagus nerve) is an unusual tumor. There are approximately 45 cases reported in the literature; the authors report four more cases. This tumor may ba associated with other paragangliomas of the head and neck, such as carotid body tumors, and may metastasize to regional lymph nodes, although the histology always appears benign.

Pseudomonas aeruginosa meningitis following stapedectomy.

Meningitis is a rare complication following stapedectomy. Most cases are preceeded by a fistula in the oval window. Although fatalities have been reported, most cases respond to parenteral and intrathecal antibiotics if diagnosed and treated early. Gram-positive organisms are the usual pathogens, but Gram-negative organisms may be found, especially as a superinfection following antibiotics administered prophylacticly or for the treatment of otitis media or mastoiditis. A case of Pseudomonas aeruginosa meningitis five weeks after stapedectomy, successfully treated with gentamicin, is reported. The discussion included the diagnosis of post-stapedectomy fistula and meningitis and current trends in treatment.

Submandibular gland tumors.

Tumors involving the submandibular gland are rare. However, the incidence of malignancy is much higher than in the parotid (approaching 50 percent). In addition, the 5-year survival rate in patients with malignant tumors of the submandibular gland is much poorer in our series--28 percent versus 71.8 percent for the parotid gland. Because of the poor prognosis in patients with malignant tumors involving the submandibular gland we feel that composite resections should be carried out for all tumors except low-grade mucoepidermoid tumors. In addition, postoperative radiation should be given for specific indications (detailed in the article).

Malignant fibrous histiocytoma of the parapharyngeal space. Case report.

Of the large variety of tumors that may occur in the parapharyngeal space, malignant fibrous histiocytoma is one of the most rare. We present such a case and discuss the diagnosis, classification, and treatment.

Intramuscular hemangioma of the masseter muscle.

We present a case of intramuscular hemangioma of the masseter muscle. We stress that, although there can be apparent vascular infiltration of the muscle, this lesion is benign; it should not be mistakenly diagnosed as an angiosarcoma.

Advanced applications of revascularized free jejunal flaps for difficult wounds of the head and neck.

The rationale, technique, and an example of full utilization of the jejunomesenteric free flap have been described as a means of reconstructing complex wounds of the head and neck. Not only jejunum, but also well-vascularized mesentery will protect vascular structures and intestinal anastomoses and, in addition, accept a skin graft. No additional muscular or other flaps are necessary to achieve these ends. Finally, no additional donor-site morbidity is incurred by harvesting the supplementary mesentery.

Cystic lesions of the parotid gland.

In a series of 708 parotidectomies (partial or total), we found 23 cystic lesions. Of these, 16 met the criteria for so-called "branchial cysts"; five were retention cysts of duct origin, and the remaining two were epidermal inclusion cysts. The principles of diagnosis and treatment of parotid cysts are presented.

Primary carcinoma of the mastoid bone.

The diagnosis of carcinoma primary in the mastoid bone is usually made while performing a mastoidectomy in an effort to control presumed chronic mastoiditis. The association of chronic infection, serosanguineous otorrhea, and severe otalgia, common warning signs of carcinoma of the middle ear or external auditory canal, may or may not be present with a carcinoma primary in the mastoid bone. If the amount of bony mastoid destruction seen by roentgenography is out of proportion to the degree of clinical infection, malignancy should be strongly suspected. The authors present a case of primary carcinoma of the mastoid bone, and review the diagnosis and treatment.