An activator protein-1 (AP-1) response element on pro alpha1(l) collagen gene is necessary for thyroid hormone-induced inhibition of promoter activity in cardiac fibroblasts.

Thyroid hormone-induced ventricular hypertrophy is characterized by the absence of fibrosis. Previously, we demonstrated that thyroid hormone inhibits collagen type I gene expression in the myocardium and in cardiac fibroblasts. We also demonstrated that thyroid hormones act as inhibitor of pro alpha1(l) collagen promoter activity. In this study we determined the sequences on pro alpha1(l) collagen gene and transcription factors in cardiac fibroblasts involved in the inhibitory effect of 3,3',5-triiodothyronine (T3). Transient transfection of cells with chloramphenicol acetyl transferase (CAT)-linked deletion mutants of pro alpha1(l) collagen promoter demonstrated that the inhibitory effect of T3 is transmitted via proximal sequences(-225/+115). Gel shift analysis using [32P]-labeled -225/+115 gene fragment and nuclear proteins of cardiac fibroblasts showed T3-induced DNA binding by two proteins. Analysis of non-overlapping restriction sub-fragments by gel shift along with supershift analysis with antibodies to types alpha and beta thyroid hormone receptors identified the lower molecular weight DNA-binding protein as beta receptor and confirmed that the T3-induced protein-DNA binding sites are located at -15/+115. Selective base mutation (C in place of G at +93 and G in place of C at +97) in the activator protein-1 (AP-1) core binding motif(+92/+97) abolished the higher molecular weight T3-induced DNA-protein complex obtained with [32P]-labeled wild type sequences (-225/+115). Additional gel shift analyses using an oligonucleotide containing the AP-1 core binding motif, as an unlabeled competitor and as [32P]-labeled probe, confirmed the T3-induced protein binding to an AP-1 site. Transient transfection with CAT-linked -225/+115 sequences in which the AP-1 site was mutated abolished the T3-induced inhibition of CAT activity. Together, these findings identify sequences necessary for T3-induced inhibition of collagen type I promoter to which thyroid hormone receptor type beta and protein(s) with affinity for AP-1 element bind. They also demonstrate that the AP-1 response element located on these sequences is necessary for T3-induced inhibition of pro alpha1(l) collagen promoter activity. These data identify molecular mechanisms involved in thyroid hormone-induced inhibition of collagen expression in the heart.

Congenital syphilis: subtle presentation of fulminant disease.

The incidence of congenital syphilis has experienced a fourfold to fivefold increase in 6 years. It is a completely preventable disease whose clinical spectrum ranges from asymptomatic infection, to fulminant sepsis, to death. Congenital syphilis was diagnosed in a 6-week-old infant whose mother was negative for the disease by prenatal screen. The otherwise well child presented with a generalized, papulosquamous eruption of 3 weeks' duration but within hours multisystem failure developed from overwhelming treponemal sepsis. Factors related to increased incidence, problems in serodiagnosis, manifestations of the early versus late forms of the disease, and recommendations for evaluation and treatment are illustrated by this patient and are discussed.

Upregulation of collagen type I gene expression in the ventricular myocardium of thyroidectomized male and female rats.

It is established that thyroxine-induced ventricular hypertrophy is associated with downregulation of collagen type I gene expression and increased collagen turnover in the ventricular tissue. The present study was undertaken to test the hypothesis that circulating thyroid hormones may have a regulatory impact on the biosynthesis of the collagen matrix in the heart. To this end, we determined collagen gene expression and deposition in the hearts of male and female Sprague-Dawley rats after surgical thyroidectomy. The serum levels of 3,3'5-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) in thyroidectomized and age/sex-matched sham-operated rats were determined by radioimmunoassay and fluorescence analysis of the serum, respectively. On day 14 post-surgery, the plasma levels of both T3 and T4 in thyroidectomized rats were decreased by greater than 85% compared with those in matching sham-operated control rats. At this time, Northern analysis of ventricular RNA from thyroidectomized rats showed a 160% (P = 0.0079) increase for pro alpha 1 (I) and a 43% increase (P = 0.0484) for pro alpha 2 (I) collagen mRNAs in the ventricular tissue of male rats compared with that in the heart of age-matched, sham-operated control rats. In the female rats, thyroidectomy led to 63% (P = 0.0469) increase in the abundance of pro alpha 1 (I) collagen and 50% (P = 0.034) increase for pro alpha 2 (I) collagen in ventricular tissue. At the protein level, the amount of collagen type I as determined by immuno-slot blotting of ventricular homogenates, was increased in the ventricular tissue of both male (131%, P = 0.0371) and female (108%, P = 0.0464) rats. Comparison of the changes in males v females showed relatively greater increases in the level of collagen type I mRNA and protein in ventricular tissue of thyroidectomized males. Of particular note, were the increases in the immunoreactive TGF-beta in ventricular tissue of thyroidectomized male and female rats which showed a pattern similar to that of changes in collagen type I. Immunofluorescent light microscopy of frozen heart sections, showed significant remodeling of the type I collagen fibers in the ventricular myocardium of thyroidectomized rats compared with age/sex-matched sham-operated rat heart. Together, these findings suggest that circulating thyroid hormones play a role in physiological regulation of collagen type I biosynthesis in the heart and this role may vary in males and females. They further suggest that normal production of collagen matrix in the heart may be dependent on the functional status of thyroid hormones.

Sweet's syndrome in children.

Acute febrile neutrophilic dermatosis (Sweet's syndrome) is a rare inflammatory disease of unknown cause characterized by painful, erythematous plaques and a dermal infiltrate of mature neutrophils. Associated systemic disease is a common finding in patients with Sweet's syndrome, and in fact determines the prognosis; therefore, the diagnosis of Sweet's syndrome warrants a thorough medical evaluation. We found only 17 reported cases of Sweet's syndrome in children. Two cases of Sweet's syndrome in children are presented; these cases are typical, except for the tibial pain in the first patient and the marked leukocytosis in the second patient. Both patients responded promptly to systemic corticosteroid therapy, although both had relapse.

Children with disabilities and the Children Act: who will assess their needs?

The Children Act focuses attention on meeting the assessed needs of children with disabilities. General practitioners (GPs) and Community Child Health (CCH) doctors in one health district were asked by postal questionnaire who it was who currently assessed such needs and who would do so in the future. The involvement of GPs (15) varied from none (1) to regular reassessment (3). Nearly all (14) treated acute illnesses but educational assessments were assigned to CCH doctors. Community doctors (9) had a clearer idea of their role including regular reassessment (9), education assessment (9) and interagency liaison (3). Both groups complained of poor communication with each other and with hospital services. To fulfil the requirements of the Children Act, community child health services, family health services authorities and district health authorities will have to specify how and by whom children with disabilities are identified and assessed. Arrangements will vary according to local service development. These arrangements, and the resulting liaison with other agencies, should be specified in National Health Service contracts, thus improving communication and cooperation.

Regulation of rat renal (Na(+) + K+)-adenosine triphosphatase mRNA levels by corticosterone.

We investigated the mechanisms for glucocorticoid regulation of rat renal NaK-ATPase activity. Our findings suggest that the magnitudes of corticosterone-induced increases in alpha 1 mRNA and beta 1 mRNA levels are similar in the kidney of the adult adrenalectomized rats. The results also suggest that corticosterone restores NaK-ATPase activity in adrenalectomized rats prior to any enhanced sodium delivery.

Follicular lymphoid hyperplasia of the hard palate: report of a case.

A review of the literature and a case report of follicular lymphoid hyperplasia (FLH) of the hard palate has been presented. This entity should always be considered when confronted with a hard-palate swelling. A diagnosis of FLH generally can be made after a thorough medical and dental examination and immunocytochemical studies of the surgical specimen. Local wide excision of the tumor is suggested as the treatment of choice. During the healing period, the use of a surgical stent will give the patient comfort as the wound heals by secondary intention.

Prescribing efficiently in nursing homes.

Giving medications in nursing homes is time consuming and expensive. The orders for medications in a community nursing home were examined to determine if nursing time could be saved by consolidating the administration of medications. Nineteen percent of the medication administration visits could be eliminated by this method according to the independent judgments of two physicians. This could save up to $19,000 in nursing time per year, and the time could be redirected to other nursing activities that could improve the quality of care in nursing homes.

Effects of triiodothyronine on resting membrane potential of primary cultured rat submandibular gland cells.

The effect of triiodothyronine (T3) on the resting membrane potential was measured in primary cultured rat submandibular gland cells. The resting membrane potential was 29.5 +/- 0.71 mV. The hormone T3, at concentrations of 10(-9) M or greater, hyperpolarized the cells 5.8 mV (p less than 0.05). Hyperpolarization was complete within 24 hours. Ouabain (1 mM) depolarized the cells 5.9 mV. Cells exposed to T3 and ouabain had the same membrane potential as cells treated with ouabain alone. These data suggest that the hyperpolarization observed can be, in part, attributed to triiodothyronine-induced synthesis of (Na-K)-adenosine triphosphatase.

Pigmented Bowen's disease and review of 420 Bowen's disease lesions.

Pigmented Bowen's disease is rare. We report an unusual case of pigmented Bowen's disease of the ring finger, which clinically presented as a superficial, spreading melanoma. Records of 420 lesions of Bowen's disease were reviewed; 7 lesions (1.67%) were pigmented and all occurred outside the anogenital area. We conclude that Bowen's disease should be considered in the differential diagnosis of pigmented lesions.

Compliance and blood pressure control.

Compliance with medical therapy in general is often low, and compliance with blood pressure treatment is no better. Numerous studies have shown that patients frequently drop out of treatment for hypertension. Furthermore, even when patients stay in treatment, they often take their medications in a way quite dissimilar from that prescribed. Identifying noncompliant patients is important but not always easy to accomplish. Pill counts, the "gold standard," are seldom practical in routine clinical practice. Assessing compliance by its biological effect is compromised by physiological diversity among patients. Assessing compliance from patient self-reports is limited in its accuracy but is more useful than many researchers and clinicians appreciate. Compliance behavior is affected by many factors. Complexity of medical regimen has some effect; the presence of drug side effects has surprisingly little. Contrary to what many clinicians think, increased age is often accompanied by increased medication compliance. Features of the doctor-patient relationship likely have an important effect on patient compliance, though our knowledge of these factors is still limited.

Medications and diagnoses in relation to falls in a long-term care facility.

The association between falls, drugs, and diagnoses in elderly residents of a long-term care facility was explored using case-control methodology. The odds of being a faller rather than a control were significant (P less than .01) for those taking antidepressants, sedatives/hypnotics, or vasodilators, and for those with osteoarthritis or depression. When drug/diagnosis subgroups were examined, these same drug classes and diagnoses had high-odds ratios in the largest numbers of subgroups. In general, risk of falling appeared to be more strongly associated with drugs than with diagnoses.

An experiment to change detection and management of mental morbidity in primary care.

A randomized clinical trial was conducted in a group practice for the primary care of adult patients to address the effect of feedback to providers of information from a psychiatric screening questionnaire, the General Health Questionnaire (GHQ). The practice is staffed by faculty, residents, and health care extenders of The Johns Hopkins University School of Medicine's Division of Internal Medicine. The patient population was drawn mainly from the inner city community in Baltimore that surrounds the hospital, where the practice is physically based. The GHQ was administered at the time of a regular visit to the practice and results made available to the clinicians for randomly allocated subsamples of their patients. The study results showed that feedback of GHQ information led to only marginal effects on overall detection of mental health problems among the patients in general. However, marked increases in detection occurred among the elderly, blacks, and men, subgroups that ordinarily have relatively low rates of detection of mental morbidity by primary care practitioners. Feedback of GHQ information did not affect management.

Detection and management of mental health problems of older patients by primary care providers.

Evidence is accruing that older individuals receive little attention for mental health problems and that any attention that is given is most often within the primary care setting. A randomized clinical trial was carried out at a primary care clinic of The Johns Hopkins University, Baltimore, testing the ability of feedback of the results of a screening instrument (the General Health Questionnaire) to increase awareness in clinicians of the emotional and psychological problems of their patients. This report contrasts those aged 65 years and older with younger patients. Detection and management of mental morbidity were lower for older individuals, but the feedback intervention increased the likelihood of attention to these problems. This was not true for younger patients. Detection was significantly higher for older patients when screening data were made available, as was management, although the latter difference was not statistically significant. There was evidence as well that the intervention moved clinicians to greater congruence with their older patients in the perception that current mental health problems existed. These findings have important implications for primary care.

Sequence of mRNA coding for bindin, a species-specific sea urchin sperm protein required for fertilization.

Bindin, a major protein of the sea urchin acrosome granule, mediates the species-specific adhesion and binding of sperm to egg required to effect fertilization. We report the isolation and sequence of bindin cDNA clones prepared from Strongylocentrotus purpuratus testis RNA. The bindin gene appears to be productively expressed only in males and only in testes. The protein is produced from a 51-kDa precursor, which is subsequently processed to yield the mature 24-kDa bindin protein.