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Biomedical subjects

L Jacobson

Publications and source records attributed to L Jacobson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effect of race on insurance coverage and health service use for HIV-infected gay men.

OBJECTIVE: To determine whether race is associated with health insurance coverage and health service use among gay and bisexual men in the Baltimore center of the Multicenter AIDS Cohort Study. METHODS: Data from eight semiannual study visits between 1991 and 1996 were used. Descriptive, stratified, and logistic regression analyses were conducted to determine whether race is associated with insurance coverage, medical, or dental service use, after controlling for socioeconomic variables. RESULTS: No difference was found between blacks' and whites' likelihood of having health insurance, private insurance, using inpatient, emergency department services, or antiretroviral medications. Whites were more likely to use outpatient services, particularly if CD4 cell counts were high, and were more likely to use dental services, although blacks were more likely to have dental insurance. CONCLUSIONS: Further research must be conducted to examine cultural, social, and psychological factors that help explain why white gay men use more outpatient and dental services, when other service use is unrelated to race. Investigators should be precise when using race as a variable in health services and epidemiologic research, emphasizing when racial differences truly exist versus when the variable race is a surrogate for another factor.

Adult↗
PubMed1999

Early-onset myasthenia gravis: a recurring T-cell epitope in the adult-specific acetylcholine receptor epsilon subunit presented by the susceptibility allele HLA-DR52a.

No immunodominant T-cell epitopes have yet been reported in the human acetylcholine receptor (AChR), the target of the pathogenic autoantibodies in myasthenia gravis (MG). We have selected and characterized T cells from MG patients by restimulation in culture with recombinant human AChR to alpha, gamma and epsilon subunits; the gamma and epsilon distinguish the fetal and adult AChR isoforms, respectively. We obtained clones specific for the epsilon, rather than the alpha or gamma, subunit in 3 of the first 4 early-onset MG cases tested. They all responded to peptide epsilon201-219 and to low concentrations of adult but not fetal AChR. Moreover, although using different T-cell receptor genes, they were all restricted to HLA-DR52a (DRB3*0101), a member of the strongly predisposing HLA-A1-B8-DR3 haplotype. This apparently immunodominant epsilon201-219 epitope (plus DR52a) was also recognized by clones from an elderly patient whose MG had recently been provoked by the drug D-penicillamine. In all 4 cases, however, the serum antibodies reacted better with fetal than adult AChR and may thus be end products of determinant spreading initiated by adult AChR-specific T cell responses. Furthermore, as these T cells had a pathogenic Th1 phenotype, with the potential to induce complement-activating antibodies, they should be important targets for selective immunotherapy.

Amino Acid Sequence↗
PubMed1999

Peripherin immunoreactivity labels small diameter vestibular 'bouton' afferents in rodents.

Recent morphophysiological studies have described three different subpopulations of vestibular afferents. The purpose of this study was to determine whether peripherin, a 56-kDa type III intermediate filament protein present in small sensory neurons in dorsal root ganglion and spiral ganglion cells, would also label thin vestibular afferents. Peripherin immunohistochemistry was done on vestibular sensory organs (cristae ampullares, utriculi and sacculi) of chinchillas, rats, and mice. In these sensory organs, immunoreactivity was confined to the extrastriolar region of the utriculus and the peripheral region of the crista. The labelled terminals were all boutons, except for an occasional calyx. In vestibular ganglia, immunoreactivity was restricted to small vestibular ganglion cells with thin axons. The immunoreactive central axons of vestibular ganglion cells form narrow bundles as they pass through the caudal spinal trigeminal tract. As they exit this tract, several bundles coalesce to form a single, narrow bundle passing caudally through the ventral part of the lateral vestibular nucleus. Finally, we conclude that all labelled axons and terminals were vestibular afferents rather than efferents, as no immunoreactivity in the vestibular efferent nucleus of the brainstem was observed.

Afferent Pathways↗
PubMed1999

Assessment of visual acuity in children aged 1 1/2-6 years, with normal and subnormal vision.

The aim of the study was to assess different visual acuity tests in the age group 1 1/2-6 years in 105 children with assumed normal vision, visual impairment due to ocular disease or strabismus. Acuity tasks for young children can be divided into three subtypes according to the kind of stimulus used. For "detection acuity", the stimulus should be detected or distinguished from the background, as assessed with the Stycar Rolling Balls. For "resolution acuity", the stimulus pattern should be resolved, as assessed with the Preferential Looking procedure (Teller Acuity Cards). For "recognition acuity", the stimulus must be recognized by the subject as assessed with the BUST-D symbol test, Sheridan Gardiner (S-G) single letters, LH single symbols and line tests, and also the HVOT test. Different acuity values were obtained with regard to detection, resolution and recognition acuities. Assessment with the Stycar Rolling Balls only gave a rough estimate of the visual function. There was an overestimation of the acuity values in all groups of children when using the Preferential Looking technique. Good agreement was found between the LH line and HVOT tests. The BUST-D test, S-G single letters, and LH single symbols gave slightly better acuity values than linear recognition tests. A "crowding ratio" was calculated by dividing the single optotype acuity by the linear acuity, and also by dividing the grating acuity by the optotype linear and single acuity. The crowding ratio varied in the individual children and in the different groups, being highest for strabismic amblyopia. The general conclusion is that reliable visual acuity measurements were not obtained until the visual acuity could be assessed with a recognition test using linear letters or symbols.

Adult↗
PubMed1999

Hereditary deficiency of vitamin-K-dependent coagulation factors in Rambouillet sheep.

A flock of Rambouillet sheep experienced unexpected lamb mortality associated with excessive bleeding at the time of parturition. Most lambs died of blood loss through the umbilicus or into subcutaneous tissues. Subsequently, nine ewes which had previously delivered lambs that bled to death were bred to the suspected sire of the previous bleeding lambs. Fifteen lambs were born alive the following Spring, and three males and one female bled clinically. These lambs had markedly decreased factor IX (< 16%) and factor X (< 4%) activities, with variably decreased factor II (11-36%) and factor VII (20-37%) activities. Protein C chromogenic activity was also markedly decreased (< 1%) in these lambs. The results from crossed immunoelectrophoresis and 'protein-induced-in-vitamin-K-absence' determination of the plasma of affected lambs, with antiserum directed against coagulation factor X, protein C or proteins S, suggested that these proteins were not carboxylated normally. Examination of liver from one lamb in the first batch and the four subsequent lambs did not reveal a known vitamin K antagonist. The breeding data suggested that the coagulopathy in these sheep was inherited as an autosomal recessive trait. The genetic or molecular defect that exists in these lambs is unknown, but possibilities include abnormal gamma-glutamyl carboxylase activity or abnormal metabolism of vitamin K.

Animals↗
PubMed1999

Glucocorticoids reverse leptin effects on food intake and body fat in mice without increasing NPY mRNA.

Glucocorticoid stimulation of appetite and leptin expression conflicts with leptin inhibition of food intake and suggests that glucocorticoids reduce sensitivity to leptin. To determine if glucocorticoids impair feeding and metabolic responses to leptin, we measured leptin-induced changes in food intake, body weight, hormones, carcass fat, and hypothalamic neuropeptide Y (NPY) mRNA in adrenalectomized mice with and without corticosterone replacement. Leptin infusion (0.5 microgram/h) significantly decreased food intake and body weight in adrenalectomized mice. Corticosterone replacement approximating normal 24-h mean levels restored food intake but did not permit weight gain equivalent to PBS-infused controls. Corticosterone levels comparable to stress-induced production completely reversed leptin-induced reductions in weight gain and body fat, despite significant attenuation by leptin of corticosterone-induced increases in plasma insulin levels. Glucocorticoid replacement increased food intake without reversing leptin inhibition of hypothalamic NPY mRNA levels. We conclude that glucocorticoid levels within the physiological range can interfere with leptin action and that glucocorticoid effects are at least partly independent of NPY.

Adipose Tissue↗
PubMed1999

Plasma from human mothers of fetuses with severe arthrogryposis multiplex congenita causes deformities in mice.

Arthrogryposis multiplex congenita (AMC) is characterized by fixed joint contractures and other deformities, sometimes resulting in fetal death. The cause is unknown in most cases, but some women with fetuses affected by severe AMC have serum antibodies that inhibit fetal acetylcholine receptor (AChR) function, and antibodies to fetal antigens might play a pathogenic role in other congenital disorders. To investigate this possibility, we have established a model by injecting pregnant mice with plasma from four anti-AChR antibody-positive women whose fetuses had severe AMC. We found that human antibodies can be transferred efficiently to the mouse fetus during the last few days of fetal life. Many of the fetuses of dams injected with AMC maternal plasmas or Ig were stillborn and showed fixed joints and other deformities. Moreover, similar changes were found in mice after injection of a serum from one anti-AChR antibody-negative mother who had had four AMC fetuses. Thus, we have confirmed the role of maternal antibodies in cases of AMC associated with maternal anti-AChR, and we have demonstrated the existence of pathogenic maternal factors in one other case. Importantly, this approach can be used to look at the effects of other maternal human antibodies on development of the fetus.

Animals↗
PubMed1999

Glucocorticoid replacement, but not corticotropin-releasing hormone deficiency, prevents adrenalectomy-induced anorexia in mice.

There is considerable evidence that CRH can suppress food intake. As hypothalamic CRH, a main site of CRH expression, is also negatively regulated by glucocorticoids, it is unclear whether anorexia and weight loss in adrenal insufficiency are attributable to elevated CRH or to decreased glucocorticoid levels. To distinguish these possibilities, we have measured food intake and body weight in wild-type and CRH-deficient mice after sham adrenalectomy (Sham ADX) or adrenalectomy (ADX) with and without corticosterone (B) replacement. CRH deficiency neither increased basal food intake and body weight nor attenuated decreases in food intake after ADX or Sham ADX. B replacement producing plasma levels above the circadian peak completely blocked ADX-induced decreases in feeding and body weight in all mice and frequently stimulated food intake in CRH-deficient mice. Plasma levels of insulin and leptin, two other hormones involved in appetite regulation, did not differ between genotypes; however, the relationship between food intake and circulating leptin was significantly less negative at B doses that preserved appetite. B replacement levels slightly below circadian peak concentrations did not prevent hypophagia after ADX. We conclude that factors other than or in addition to CRH are more important in mediating appetite responses to adrenalectomy.

Adrenalectomy↗
PubMed1999

Normal suppression of the reproductive axis following stress in corticotropin-releasing hormone-deficient mice.

The hypothalamic neuropeptide CRH has been postulated to inhibit LH secretion by a central action within the brain. To characterize the physiological significance of CRH in stressor-induced inhibition of LH secretion, CRH-deficient and wild-type mice were subjected to restraint or food withdrawal, and plasma LH levels were determined. The proestrus LH surge of female mice was equally suppressed by restraint in both genotypes, and central administration of a CRH antagonist did not alleviate this suppression in either genotype. Male mice of both genotypes also demonstrated suppression of both LH and testosterone secretion following restraint. Furthermore, food withdrawal caused similar suppression of LH secretion in both female and male mice regardless of CRH status. These data demonstrate that CRH is not necessary to inhibit LH secretion following either restraint or food withdrawal and that other molecules are able to suppress LH secretion during the response to stress in the context of CRH deficiency.

Animals↗
PubMed1999

Lower weight loss and food intake in protein-deprived, corticotropin releasing hormone-deficient mice correlate with glucocorticoid insufficiency.

To determine if CRH and glucocorticoids are respectively required for hypophagia and catabolism in malnutrition, we have subjected wild-type (WT) and CRH knockout (KO) mice to dietary protein deprivation. Compared with WT mice, CRH KO mice exhibited greater decreases in food intake and negligible change in plasma corticosterone after 7 days of protein-free diet. Restricting consumption of normal or protein-free diet for 9 days to the lower intake in protein-deprived CRH KO mice increased evening plasma corticosterone in WT but not KO mice. Restricted intake of protein-free diet increased morning corticosterone more in both genotypes than restricted intake of normal diet, although corticosterone levels were much lower in CRH KO mice. CRH deficiency attenuated body and thymus weight loss induced by restricted diets. Lower weight loss in CRH KO mice was associated with lower fractional loss of body water and protein. The remaining catabolic response in CRH KO mice did not correlate with morning plasma catecholamines or insulin. Corticosterone, but not the progestational appetite stimulant megestrol acetate, prevented hypophagia in CRH KO mice given protein-free diet. We conclude that differences in feeding and metabolic responses to protein deprivation between WT and CRH KO mice are primarily attributable to glucocorticoid insufficiency.

Animals↗
PubMed1998

Antibodies affecting ion channel function in acquired neuromyotonia, in seropositive and seronegative myasthenia gravis, and in antibody-mediated arthrogryposis multiplex congenita.

A new autoimmune disease affecting the neuromuscular junction has been defined. Acquired neuromyotonia is associated with antibodies to voltage-gated potassium channels that act, at least in part, by reducing potassium channel function with resulting neuronal hyperactivity. This condition is quite frequently associated with thymoma and, in many cases, antibodies to acetylcholine receptors are present as well as antibodies to VGKC. Improvements in techniques and the availability of cloned DNA and recombinant forms of the AChR subunits have led to new observations concerning the specificity and roles of antibodies in myasthenia gravis. The transfection of a cell line with the epsilon subunit means that we can now accurately compare antibodies reactive with adult and fetal human AChR. This may help to determine the relationship between AChR subunit expression in different tissues and the induction of antibodies that bind specifically to the two forms, as well as to clarify the role of antibodies to fetal or adult AChR in causing ocular muscle symptoms. Serum antibodies from a few mothers with obstetric histories of recurrent arthrogryposis multiplex congenita in their babies specifically inhibit the function of fetal AChR. These observations not only explain the cause of some cases of arthrogryposis multiplex congenita, but also suggest that other fetal-specific antibodies might be responsible for other fetal or neonatal conditions. An animal model has been established to enable us to investigate the role of maternal serum factors in causing such disorders. Seronegative MG has been the subject of many studies from our laboratory over the last ten years. The transience of the effects of SNMG plasmas on AChR function strongly suggests that the plasma antibodies do not bind directly to the AChR, but inhibit function by some indirect mechanism. They do not appear to act via the cAMP-dependent protein kinase pathway, and studies are in progress to investigate the involvement of other second messenger systems.

Adult↗
PubMed1998

Recognising meningococcal disease in primary care: qualitative study of how general practitioners process clinical and contextual information.

OBJECTIVES: To describe the presentation of meningococcal disease in primary care; to explore how general practitioners process clinical and contextual information in children with meningococcal disease; and to describe how this information affects management. DESIGN: Qualitative analysis of semistructured interviews. SETTING: General practices in South Glamorgan. SUBJECTS: 26 general practitioners who between January 1994 and December 1996 admitted 31 children (under 16 years of age) in whom meningococcal disease was diagnosed. MAIN OUTCOME MEASURES: Categories of clinical rules and techniques used by general practitioners in processing each case. RESULTS: 22 children had rashes; in 16 of them the rashes were non-blanching. When present, a haemorrhagic rash was the most important factor in the doctor's decision to admit a child. 22 children had clinical features not normally expected in children with acute self limiting illnesses--for example, lethargy, poor eye contact, altered mental states, pallor with a high temperature, and an abnormal cry. Contextual information, such as knowledge of parents' consultation patterns and their normal degree of anxiety, played an important part in the management decisions in 15 cases. Use of penicillin was associated with the certainty of diagnosis and the presence and type of haemorrhagic rash. CONCLUSION: The key clinical feature of meningococcal disease--a haemorrhagic rash--was present in only half of the study children. The general practitioners specifically hunted for the rash in some ill children, but doctors should not be deterred from diagnosing meningococcal disease and starting antibiotic treatment if the child is otherwise well, if the rash has an unusual or scanty distribution, or if the rash is non-haemorrhagic.

Adolescent↗