Interaction of transforming growth factor β1 with human glomerular epithelial cells in culture: opposite effects on synthesis of matrix proteins and on urokinase plasminogen activator

The effect of transforming growth factor- (TGF-) was analyzed on the synthesis of fibronectin, collagen type IV, and urokinase plasminogen activator in human glomerular epithelial cells in culture. An increase in the abundance of specific mRNA was found for collagen type IV and fibronectin. Fibronectin protein synthesis was also increased in TGF- treated cells; most of the de novo synthesized fibronectin was found as an unsoluble protein associated with extracellular matrix. In the same cells the amount of plasminogen activator mRNA was found leading also to a decreased surface expression of urokinase plasminogen activator. The data support the concept that by upregulating matrix protein synthesis and downregulating the plasminogen activator system, TGF- favors the development of sclerosis.Abbreviations FN Fibronectin - GEC Glomerular epithelial cells - TGF- Transforming growth factor - uPA Urokinase-type plasminogen activator     

The increased needs of patients in nursing homes and patients receiving home health care

To evaluate the effects of Medicare's prospective payment system and Medicaid's preadmission regulations on long-term care, we constructed clinical profiles in 1982 and 1986 of about 500 randomly selected patients from each of three types of facilities: nursing homes with relatively high proportions of Medicare patients (high-Medicare nursing homes; n = 23), traditional nursing homes (n = 19), and home health agencies (n = 18). Data were obtained directly from the care givers on the medical problems, problems requiring skilled nursing, and functional problems of these representative patients from 12 states. For Medicare patients in high-Medicare nursing homes, the prevalence of medical problems and problems requiring skilled nursing increased substantially, whereas the prevalence of functional problems remained relatively unchanged. For example, from 1982 to 1986 there was a marked increase in the frequency of tube feedings (21 to 29 percent), oxygen use (6 to 14 percent), urinary tract infection (7 to 13 percent), and diastolic hypertension (1 to 10 percent), but not difficulty in eating (48 to 51 percent) or speaking (28 to 29 percent). In contrast, in traditional nursing homes there was an increase in the prevalence of functional disability, but virtually no change in that of problems requiring medical and skilled nursing care. In home health care the functional care needs of Medicare patients increased significantly, and there was a slight increase in the prevalence of problems requiring medical and skilled nursing care. We conclude that from 1982 to 1986 the needs of patients in long-term care increased substantially. This trend appears to result from Medicare's prospective payment system, which encourages earlier hospital discharge to long-term care settings, and from Medicaid's policy of de-institutionalization. Meeting this greater need for care will be costly. We require a better system of reimbursing for long-term care and ensuring its quality.     

Cystic fibrosis: Synthesis of ciliary inhibitor by amniotic cells

The presence of a ciliary inhibitor in media of cultured amniotic cells obtained from a fetus heterozygous for cystic fibrosis has been observed by the oyster gill cilia assay. The chromatographic fraction containing the inhibitor corresponded to eluted fractions chromatographed from cystic fibrosis fibroblast media and serum. An analogous chromatographic fraction from media of cultured amniotic cells from two proportedly normal fetuses did not inhibit cilia. The chromatographic fraction from media of cultured amniotic cells of a fetus at high risk for cystic fibrosis did not inhibit ciliary activity. Serum was collected from this baby seven weeks after birth and also did not inhibit ciliary action, indicating a homozygous normal genotype. These observations may lead to the development of an antenatal test for cystic fibrosis.     

Increased frequency of congenital chromosomal aberrations in female partners of couples undergoing intracytoplasmic sperm injection

We evaluated the frequency of congenital chromosomal aberrations in a sample of 305 couples included in an intracytoplasmic sperm injection (ICSI) programme. Twenty individuals (3.3%) with congenital chromosomal abnormalities could be identified. The following types of abnormalities were observed: reciprocal translocations (n = 7), Robertsonian translocations (n = 3), inversions (n = 3), other structural aberrations (n = 4) and sex chromosome aberrations (n = 3). The rate of chromosomally abnormal males (10/305, 3.3%) lay within the expected range for patients with reduced semen quality. Surprisingly, 50% (10/20) of all abnormal karyotypes were contributed by the female partner of ICSI patients. These data confirm the higher incidence of chromosomal aberrations in infertile populations as compared with the baseline population risk. Additionally, the data imply that in some cases of male factor infertility a hidden female chromosomal factor may be present, which cannot be identified by standard clinical evaluation. In conclusion, we recommend chromosomal analysis in both partners of couples undergoing ICSI treatment.      

Identification of a gene disrupted by a microdeletion in a patient with X-linked retinitis pigmentosa (XLRP)

The gene for the most frequent from of X-linked retinitis pigmentosa (XLRP), RP3, has been assigned by genetic and physical mapping to a segment of less than 1000 kbp, which is flanked by the marker DXS1110 and the ornithine transcarbamylase (OTC) gene. In search of microdeletions, we have screened the DNA of 30 unrelated patients with XLRP by employing a representative set of YAC-derived DNA fragments that were generated by restriction enzyme digestion and PCR amplification. In one of these patients, a 6.4 kbp microdeletion was detected which was not present in the DNA of 444 male controls. A cosmid contig spanning the deletion was constructed and used to isolate cDNAs from retina-specific libraries. Exons corresponding to these expressed sequences as well as other putative exons were identified by sequencing more than 30 kbp of the critical region. So far, no point mutations in these putative exon sequences have been identified.      

Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1

The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X- linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization (YRH)', we have recently identified a small XLRP associated microdeletion in this interval, as well as several putative exons including the 3' end of a gene that was truncated by the deletion. cDNA library screening and sequencing of a cosmid centromeric to the deletion has now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene product shows homology to RCC1, the guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our findings suggest that we have cloned the long-sought RP3 gene, and that it may encode the GEF of a retina-specific GTP-binding protein.      

An octosporeosis of the black blowfly,Phormia regina: Incidence rates of host and parasite

Summary Adult black blowflies Phormia regina were trapped from April through October in Urbana, Illinois for the years 1963 and 1964. Samples of flies from each catch were examined for the presence of the microsporidian parasite Octosporea muscaedomesticae. In 1963, the monthly parasite incidence rate steadily increased with the progression of the seasons while the fly population declined over the same period. In 1964, the monthly parasite incidence rate followed no decernable pattern; this was probably attributable to the fact that the host remained comparatively scarce for the entire period following heavy spring rains. The observed monthly parasite incidence rates ranged from zero to 13% over the two-year period. The annual parasite incidence rate was 4% in 1963 and 4.5% in 1964. No significant differences were found in the parasite incidence rates of females versus males. The observed parasite incidence rates, while indicative of general trends, probably are lower than the actual rates in nature. Reasons for this are discussed. Finally it is suggested that O. muscaedomesticae may at times act as a suppressor of P. regina populations in the field.

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Zusammenfassung Erwachsene Fliegen der Art Phormia regina wurden vom April bis Oktober in Urbana, Illinois, in den Jahren 1963 und 1964 gefangen. Einige Fliegen aus jedem Fang wurden auf Microsporidien der Art Octosporea muscaedomesticae untersucht. Im Jahre 1963 erhöhte sich die monatliche Infektionsrate ständig mit dem Fortschreiten des Jahres, während sich die Fliegenpopulation in derselben Periode verminderte. Im Jahre 1964 war eine solche Beziehung nicht erkennbar; dieser Umstand wird darauf zurückgeführt, daß der Wirt während der ganzen folgenden Periode der schweren Frühlingsregenfälle relativ spärlich auftrat. Die beobachtete monatliche Parasitenhäufigkeit wechselte während der 2-Jahresperiode zwischen 0 und 13%. Die jährliche Parasitenhäufigkeit lag 1963 bei 4% und im Jahre 1964 bei 4,5%. Es war keine significante Differenz in der Parasitenhäufigkeit zwischen weiblichen und männlichen Tieren festzustellen. Die beobachtete Parasitenhäufigkeit war, wenn man den generellen Trend betrachtet, wahrscheinlich eher geringer als die aktuelle Rate in der freien Natur. Die Gründe für diese Umstände werden diskutiert. Schließlich wird angenommen, daß sich O. muscaedomesticae als ein begrenzender Faktor (supressor) für P. regina Population in der freien Natur anzusehen ist.

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This study was supported in part by Research Grant AI-05068 from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, U.S. Public Health Service.     

Practice parameters for the indications for polysomnography and related procedures: an update for 2005

These practice parameters are an update of the previously-published recommendations regarding the indications for polysomnography and related procedures in the diagnosis of sleep disorders. Diagnostic categories include the following: sleep related breathing disorders, other respiratory disorders, narcolepsy, parasomnias, sleep related seizure disorders, restless legs syndrome, periodic limb movement sleep disorder, depression with insomnia, and circadian rhythm sleep disorders. Polysomnography is routinely indicated for the diagnosis of sleep related breathing disorders; for continuous positive airway pressure (CPAP) titration in patients with sleep related breathing disorders; for the assessment of treatment results in some cases; with a multiple sleep latency test in the evaluation of suspected narcolepsy; in evaluating sleep related behaviors that are violent or otherwise potentially injurious to the patient or others; and in certain atypical or unusual parasomnias. Polysomnography may be indicated in patients with neuromuscular disorders and sleep related symptoms; to assist in the diagnosis of paroxysmal arousals or other sleep disruptions thought to be seizure related; in a presumed parasomnia or sleep related seizure disorder that does not respond to conventional therapy; or when there is a strong clinical suspicion of periodic limb movement sleep disorder. Polysomnography is not routinely indicated to diagnose chronic lung disease; in cases of typical, uncomplicated, and noninjurious parasomnias when the diagnosis is clearly delineated; for patients with seizures who have no specific complaints consistent with a sleep disorder; to diagnose or treat restless legs syndrome; for the diagnosis of circadian rhythm sleep disorders; or to establish a diagnosis of depression.