Culture and characterization of sinusoidal endothelial cells isolated from human liver

BACKGROUND: Epidemiologic data concerning skin diseases in many rural areas in sub-Saharan Africa are not available. Little is known about the effect of regular treatment schedules by paramedical staff (especially community health workers) in the primary healthcare system on the severity and prevalence of dermatoses. METHODS: 5780 school and pre-school children from 13 primary schools in four sublocations in rural western Kenya (Kisumu District) were examined for dermatoses by the author, together with community health workers in 1993. On-the-spot training and weekend seminars about important and common dermatoses were also given. In 1994 a dermatology program was started within the primary healthcare system. Twelve trained community health workers carried out regular school visits once a week and diagnosed and treated pupils with dermatoses. Treatment was performed with gentian violet 1% solution for bacterial skin infections, Whitfield's ointment for dermatophytoses, benzylbenzoate emulsion 25% for scabies, and hydrocortisone acetate 1% cream for eczemas. All schools were visited again in 1995 to evaluate the long-term effects of the program. RESULTS: In 1993, the prevalence rate for dermatoses was 32.4%. Most of the skin diseases found were of infective origin (27.1% were caused by bacteria, 21.6% by fungi, and 17.6% by arthropods, mainly scabies mites). Dermatitis accounted for 3.5%. In 1995, the prevalence of dermatoses declined to 29.6% (p<0.05), and this reduction was most strongly observed for tropical ulcers and tinea capitis. Additionally, there was an improvement in the extent and severity of skin diseases. CONCLUSIONS: This study defines, for the first time, the number and extent of skin diseases in children in rural Kisumu District; most dermatoses were of infective origin. The study demonstrates that community health workers in the primary healthcare system are capable of dealing successfully with the most common dermatoses in children following a short training period.     

HLA-B27-restricted antigen presentation in the absence of tapasin reveals polymorphism in mechanisms of HLA class I peptide loading

Tapasin is a resident ER protein believed to be critical for antigen presentation by HLA class I molecules. We demonstrate that allelic variation in MHC class I molecules influences their dependence on tapasin for peptide loading and antigen presentation. HLA-B*2705 molecules achieve high levels of surface expression and present specific viral peptides in the absence of tapasin. In contrast, HLA-B*4402 molecules are highly dependent upon human tapasin for these functions, while HLA-B8 molecules are intermediate in this regard. Significantly, HLA-B*2705 like HLA-B*4402, requires tapasin to associate efficiently with TAP (transporters associated with antigen processing). The unusual ability of HLA-B*2705 to form peptide complexes without associating with TAP or tapasin confers flexibility in the repertoire of peptides presented by this molecule. We speculate that these properties might contribute to the role of HLA-B27 in conferring susceptibility to inflammatory spondyloarthropathies.     

A prospective study of the efficacy of the physician order form for life-sustaining treatment

OBJECTIVES: The Physician Orders for Life-Sustaining Treatment (POLST), a comprehensive, one-page order form, was developed to convey preferences for life-sustaining treatments during transfer from one care site to another. This study examined the extent to which the POLST form ensured that nursing home residents' wishes were honored for Do Not Resuscitate (DNR) and requests for transfer only if comfort measures fail. DESIGN: The study used chart record data to follow prospectively a sample of nursing home residents with the POLST. SETTING: Eight geographically diverse, long-term, adult-care facilities in Oregon in which the POLST was in use. PARTICIPANTS: Nursing home residents (n = 180), who had a POLST recording DNR designation and who indicated a desire for transfer only if comfort measures failed, were followed for 1 year. MEASUREMENTS: For all subjects: treatment and disposition after significant health status changes; orders for narcotics and for provision or limitation of aggressive interventions. For hospitalized subjects: diagnosis, medical interventions, and DNR orders. For those who died: cause and location of death, life-sustaining treatments attempted, and comfort measures provided. RESULTS: No study subject received CPR, ICU care, or ventilator support, and only 2% were hospitalized to extend life. Of the 38 subjects who died during the study year, 63% had an order for narcotics, and only two (5%) died in an acute care hospital. A total of 24 subjects (13%) were hospitalized during the year. Hospitalized subjects' mean length of stay was 4.9 days, and the mean rate of hospitalizations for all subjects was 174 per 1000 resident years. In 85% of all hospitalizations, patients were transferred because the nursing home could not control suffering. In 15% of hospitalizations (n = 4), the transfer was to extend life, overriding POLST orders. CONCLUSIONS: POLST orders regarding CPR in nursing home residents in this study were universally respected. Study subjects received remarkably high levels of comfort care and low rates of transfer for aggressive life-extending treatments.     

Transporters for cationic amino acids in animal cells: discovery, structure, and function

The structure and function of the four cationic amino acid transporters identified in animal cells are discussed. The systems differ in specificity, cation dependence, and physiological role. One of them, system y+, is selective for cationic amino acids, whereas the others (B[0,+], b[0,+], and y+ L) also accept neutral amino acids. In recent years, cDNA clones related to these activities have been isolated. Thus two families of proteins have been identified: 1) CAT or cationic amino acid transporters and 2) BAT or broad-scope transport proteins. In the CAT family, three genes encode for four different isoforms [CAT-1, CAT-2A, CAT-2(B) and CAT-3]; these are approximately 70-kDa proteins with multiple transmembrane segments (12-14), and despite their structural similarity, they differ in tissue distribution, kinetics, and regulatory properties. System y+ is the expression of the activity of CAT transporters. The BAT family includes two isoforms (rBAT and 4F2hc); these are 59- to 78-kDa proteins with one to four membrane-spanning segments, and it has been proposed that these proteins act as transport regulators. The expression of rBAT and 4F2hc induces system b[0,+] and system y+ L activity in Xenopus laevis oocytes, respectively. The roles of these transporters in nutrition, endocrinology, nitric oxide biology, and immunology, as well as in the genetic diseases cystinuria and lysinuric protein intolerance, are reviewed. Experimental strategies, which can be used in the kinetic characterization of coexpressed transporters, are also discussed.     

Adrenergic receptors and secretory responses of the rat submandibular salivary gland after periodic incisor reduction

While loss-of-function mutations in Gsalpha are invariably associated with the short stature and brachydactyly of Albright hereditary osteodystrophy (AHO), the association with hormone resistance (to parathyroid hormone and thyrotropin) typical of pseudohypoparathyroidism type Ia (PHP-Ia) is much more variable. Observational studies and DNA polymorphism analysis suggest that maternal transmission of the Gsalpha mutation may be required for full expression of clinical hormone resistance. To test this hypothesis, we studied transmission of a frameshift mutation in Gsalpha through three generations of a pedigree affected by AHO and PHP-Ia. While all family members carrying this loss-of-function mutation in one Gsalpha allele had AHO, neither the presence of the mutation nor the degree of reduction of erythrocyte Gsalpha bioactivity allowed prediction of phenotype (AHO alone versus AHO and PHP-Ia). Paternal transmission of the mutation (from the patriarch of the first generation to three members of the second generation) was not associated with concurrent PHP-Ia, but maternal transmission (from two women in the second generation to four children in the third generation) was invariably associated with PHP-Ia. No expansion of an upstream short CCG nucleotide repeat region was detected, nor was there evidence of uniparental disomy by polymorphism analysis. This report, the first to document the effects across three generations of both paternal and maternal transmission of a specific Gsalpha mutation, strongly supports the hypothesis that a maternal factor determines full expression of Gsalpha dysfunction as PHP-Ia.     

Interface potential of calcium phosphate in simulated body fluid

Calcium phosphate ceramics are used in the substitution of injured or damaged bones. Nevertheless, the behaviour of these materials, and in particular, the mechanisms guiding their interface response in physiological environment is still unknown. This work describes the construction of hydroxyapatite and tricalcium phosphate electrodes used to determine the interface potential behaviour of these materials in a simulated body fluid, in a pH range corresponding to the variation observed in human body injuries, at ambient and physiological temperatures. These measurements are associated with the adsorption/desorption of ions from the materials. The results show that hydroxyapatite and tricalcium phosphate have similar behaviour in that they reach an interface potential equilibrium state faster when the solution pH is decreased and the temperature increased. This behaviour may be attributed to their ability to form a calcium-rich layer and is relevant to their quality as implantable materials.     

Relaxin and decidualization in mice: a reappraisal

The nature of the physiological stimulus inducing decidualization in the endometrium is unknown. In this study we attempted to verify a recent report that relaxin can induce decidualization in intact mice primed with a high dose of estradiol valerate (5 micrograms) and a low dose (10 micrograms) of medroxyprogesterone acetate. In our study, neither s.c. nor intrauterine relaxin, nor intraluminal arachis oil, (an established deciduogenic stimulus) were able to induce decidualization. In addition, while oil was able to induce decidualization (increased uterine weight, and positive Pontamine Sky Blue and stromal alkaline phosphatase reactions) in ovariectomized mice treated with a regimen of estradiol and medroxyprogesterone acetate designed to produce optimum uterine sensitivity, no decidualization occurred in response to either s.c. or intraluminal relaxin. This study fails to provide any support for a role for relaxin as a deciduogenic stimulus.     

Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens

The electroencephalographic abnormalities seen in Landau-Kleffner syndrome (LKS) (language deterioration) are non-specific, and consist of a variety of epileptiform discharge patterns including continuous slow spike-wave discharges during sleep, focal sharp waves with spikes, and centrotemporal (rolandic) spikes. Similarly, the EEG abnormalities seen in autistic epileptiform regression (language and social/behavioral deterioration) are non-specific and overlap with those seen in LKS. By contrast, distinct epilepsy syndromes in otherwise normal children occur in the EEG-defined benign focal epilepsies of childhood. Occipital spikes or spike-wave present either in the older child with visual symptoms and headache or in the younger child with autonomic symptoms followed by brief or prolonged partial motor seizures. Seven young children (five from a consecutive series of 42) presenting clinically with autism or autistic regression and possible or definite seizures, whose EEGs revealed occipital spikes or spike-wave characteristic of the benign epilepsies, are reported. Although occipital spikes are commonly seen in young children as an age-dependent EEG-defined benign focal epilepsy, their high frequency in this population with cognitive difficulties suggests a possible causal relation. The effects of the epileptiform discharge on cognitive functioning presumably reflect extension into temporal and parietal lobes, rather than occipital disturbances per se.