Uncoupling protein-1 mRNA expression in lipomas from patients bearing pathogenic mitochondrial DNA mutations

Multiple symmetric lipomatosis (MSL) is a rare disorder characterised by large subcutaneous fat masses in some parts of the trunk. Mitochondrial disfunction is common in MSL, but the identity of the adipose cells developing in multiple lipomas is not well known. We determined that brown adipose tissue-specific uncoupling protein-1 (UCP-1) mRNA is expressed in the lipoma of a multiple symmetric lipomatosis patient bearing the 8344 mutation in the tRNALys gene of mitochondrial DNA. UCP1 mRNA was not detected in normal subcutaneous fat from the same patient or in the lipoma of another patient bearing a different mutation in the same tRNALys gene. These findings implicate brown adipose cells as the origin of lipomas in a subset of patients bearing tRNALys mutations in mitochondrial DNA.     

Adipocyte adenylate cyclase and alpha- and beta-adrenergic receptors in one case of multiple symmetric lipomatosis

Adenylate cyclase activity and the number of alpha- and beta-adrenergic receptors (studied by radioligand binding techniques) were compared to adipocyte membranes prepared from lipomatous and normal adjacent adipose tissue of a patient with multiple symmetric lipomatosis. No difference could be detected between the normal and lipomatous adipose biopsies. These data strongly suggest that the impairement of catecholamine-induced lipolysis often reported in lipomas is related to a defect in the enzymatic steps localized beyond rather than before cyclic AMP synthesis.     

Mitochondrial DNA mutations in multiple symmetric lipomatosis

Multiple symmetric lipomatosis (MSL) is a rare disorder of middle life characterized by large subcutaneous fat masses around the neck, shoulders and other parts of the trunk. Peripheral neuropathy is a common finding in these predominantly male patients. Employing electrophysiological measures, we found additional signs of central nervous system involvement in a majority of patients. Etiologically, there is an association with mitochondrial dysfunction. In muscle biopsy, we found ragged red fibers in 8 of 12 patients. Molecular genetic analysis revealed multiple deletions of mitochondrial DNA in one patient and the MERRF mutation at nucleotide 8344 in another. In this review, we summarize our clinical, electrophysiological morphological, biochemical and molecular genetic findings in 17 MSL patients, and give a survey of the literature. (Mol Cell Biochem 174: 271–275, 1997)     

Minimally invasive approach to familial multiple lipomatosis

Thirty-five abdominal wall lipomas were removed from a patient with familial multiple lipomatosis using a minimally invasive approach in a cost-effective, reliable, and cosmetically pleasing manner. The surgical technique used is described in this case report. Clinical findings and prior excisions provided the preoperative diagnosis. The abdominal wall was dissected through two small, vertical midline incisions in the suprafascial plane with the aid of a lighted breast retractor. A complete excision of all palpable lipomas was achieved with this approach. The patient had excellent cosmetic results with minimal postoperative scarring.     

Facial infiltrating lipomatosis.

Facial infiltrating lipomatosis is a rare congenital disorder in which mature lipocytes invade adjacent tissue. The phenotypic features include soft-tissue and skeletal hypertrophy, premature dental eruption, and regional macrodontia. There is a high risk for regrowth after resection that is, perforce, subtotal. The etiology, natural history, optimal management, and relationship to other disorders of fatty overgrowth are unclear. In this study, the clinical features, radiographic findings, histopathology, and postoperative results were analyzed in 13 patients with facial infiltrating lipomatosis. The condition was diagnosed in infancy (eight male subjects, five female subjects) and characterized by enlargement of the cheek (n = 12) or chin (n = 1). Other findings included cutaneous capillary blush (n = 9), ipsilateral macroglossia (n = 8), and mucosal neuromas (n = 6). Most patients had early eruption of ipsilateral deciduous and permanent teeth (n = 12). Computed tomography and magnetic resonance imaging showed an infiltrated soft-tissue mass of fatty density (n = 13) and skeletal overgrowth (n = 9). Multiple resection was performed on six patients (mean number of operations per patient, 2.5; range, one to six operations); regrowth and/or worsening of the capillary stain occurred in all six patients. Because surgical removal of the mass is usually unsuccessful, specific management of this condition will require insight into its etiopathogenesis. Given the presence of mucosal neuromas and lipomatosis, this study included testing for the known mutations in three entities that are associated with these soft-tissue findings (Cowden syndrome, Bannayan-Riley-Ruvalcava syndrome, and multiple endocrine neoplasia type 2B). Results of DNA analyses for these germline mutations were negative. It is more likely that this disorder is caused by a somatic mutation involving a local increase in growth factor(s).     

Adenylate cyclase of multiple lipomata. Regional differences in adrenaline-responsiveness

Multiple symmetric lipomatosis has been proposed to be associated with impaired catecholamine-responsiveness of hypertrophic adipose tissue at the level of beta-adrenergic receptors or adenylate cyclase respectively. We have studied the regulation of the adenylate cyclase by guanine nucleotides and adrenaline in 5 subjects suffering from multiple encapsulated lipomata. In the presence of GTP (0.1 mmol/l) basal adenylate cyclase activity averaged 0.5 +/- 0.3 nmol cAMP/mg protein/10 minutes in normal adipose tissue and 1.0 +/- 0.4 nmol cAMP/mg protein/10 minutes in hypertrophic adipose tissue respectively. The synthetic GTP-analogue GMP(PNP) (0.1 mmol/l) increased non-stimulated activity by about 100% in both tissues. Adrenaline (1 mumol/l-1 mmol/l) caused a dose-dependent increase of enzymic activity in both tissues which had a maximum of 130% above basal levels in the presence of GTP and of 300% in the presence of GMP(PNP) respectively. In one of the six subjects suffering from gluteal lipomata normal adipose tissue was obtained from the gluteal as well as the abdominal region on two occasions. Maximally effective concentrations of adrenaline (1 mmol/l) induced a 3-fold increase of enzymic activity in abdominal membranes compared with about a 1.7- and 1.75-fold increase in normal and lipomatous tissue from the gluteal region. The results show that encapsulated lipomata contain a normally reactive adenylate cyclase system.     

Crossed renal ectopia with pelvic lipomatosis: a new syndrome involving chromosome 1

Summary An 18-year-old male patient is described who possesses both kidneys on one side (crossed renal ectopia), together with pelvic lipomatosis. In general, lipomatosis is benign, but here the tissue shows the rare feature of malignancy. Chromosomally, the patient is typically characterised by somatic translocations involving chromosome 1 (37% metaphases); these almost always exhibit a whole chromosome translocation with chromosome 6 (35%), although involvement of chromosome 1 with chromosome 8 is present in 2% of metaphases. Other chromosomal features encountered in Giemsastained and G-banded preparations from lymphocyte cultures include the prevalence of a small Y chromosome in 25% of metaphases, the presence of marker dots in 20%, and acrocentric associations in 8%–10% of metaphases. However, more than 50% of metaphases have a normal 46 XY karyotype with a normal-sized Y-chromosome. Crossed renal ectopia with pelvic lipomatosis can therefore be assigned to a new syndrome characterised by a whole-chromosome translocation involving chromosomes 1 and 6.     

Kinetics of hog pancreas alpha-amylase; theoretical model of the dual-site enzyme

The model of the multiple attack mechanism has been proposed for the enzyme consisting of two hypothetical subunits or domains identical in structure and function. The theoretical coefficients of multiple attack: effectiveness and average number of unitary movements, have been computed for such a dual-site model of pancreatic alpha-amylase. Those coefficients affect the values of maximum velocity and Michaelis constant, respectively. Two possible manners of the subunit coupling were considered: symmetric and sequential. The dual-site model with a symmetric type of coupling appeared to be kinetically indistinguishable from the single-site model.     

Experimental model of atherosclerosis induced by administration of acetylcholine into the reticular formation of the midbrain

Acetylcholine injections into the mesencephalon reticular system of rabbits every second day during a month induced atherosclerosis of the aorta. The microscopic examination of aortic intima showed lipomatosis, liposclerosis, atheromatosis, atherocalcinosis.     

A theory of natural selection incorporating interaction among individuals. VIII. Use of groups consisting of a sire and several dams

The previous paper, (VII), in this series dealt with a group structure that consisted of a single mating pair. It was demonstrated that selection operating on such groups produced optimum short- and long-term results. The present study extends this group structure to include a single sire and several, (n ? 1), dams. The objective of the present study is to determine whether or not the optimum evolutionary results inherent with groups consisting of a single mating pair extend to groups consisting of multiple matings.It is demonstrated that extending the group from a single mating pair to include multiple matings converts the strictly symmetric into a modified-symmetric selection procedure that combines symmetric and non-symmetric properties. Thus the optimum evolutionary results of groups consisting of a single mating pair do not extend completely to groups consisting of multiple matings.     

The Molecular Signature of HIV-1-Associated Lipomatosis Reveals Differential Involvement of Brown and Beige/Brite Adipocyte Cell Lineages

Highly active antiretroviral therapy has remarkably improved quality of life of HIV-1-infected patients. However, this treatment has been associated with the so-called lipodystrophic syndrome, which conveys a number of adverse metabolic effects and morphological alterations. Among them, lipoatrophy of subcutaneous fat in certain anatomical areas and hypertrophy of visceral depots are the most common. Less frequently, lipomatous enlargements of subcutaneous fat at distinct anatomic areas occur. Lipomatous adipose tissue in the dorso-cervical area (“buffalo hump”) has been associated with a partial white-to-brown phenotype transition and with increased cell proliferation, but, to date, lipomatous enlargements arising in other parts of the body have not been characterized. In order to establish the main molecular events associated with the appearance of lipomatosis in HIV-1 patients, we analyzed biopsies of lipomatous tissue from “buffalo hump” and from other anatomical areas in patients, in comparison with healthy subcutaneous adipose tissue, using a marker gene expression approach. Both buffalo-hump and non-buffalo-hump lipomatous adipose tissues exhibited similar patterns of non-compromised adipogenesis, unaltered inflammation, non-fibrotic phenotype and proliferative activity. Shorter telomere length, prelamin A accumulation and SA-β-Gal induction, reminiscent of adipocyte senescence, were also common to both types of lipomatous tissues. Buffalo hump biopsies showed expression of marker genes of brown adipose tissue (e.g. UCP1) and, specifically, of “classical” brown adipocytes (e.g. ZIC1) but not of beige/brite adipocytes. No such brown fat-related gene expression occurred in lipomatous tissues at other anatomical sites. In conclusion, buffalo hump and other subcutaneous adipose tissue enlargements from HIV-1-infected patients share a similar lipomatous character. However, a distorted induction of white-to-“classical brown adipocyte” phenotype appears unique of dorso-cervical lipomatosis. Thus, the insults caused by HIV-1 viral infection and/or antiretroviral therapy leading to lipomatosis are acting in a location- and adipocyte lineage-dependent manner.     

Conduction properties of the cloned Shaker K+ channel.

The conduction properties of the cloned Shaker K+ channel were studied using electrophysiological techniques. Single channel conductance increases in a sublinear manner with symmetric increases in K+ activity, reaching saturation by 0.6 M K+. The Shaker K+ channel is highly selective among monovalent cations; under bi-ionic conditions, its selectivity sequence is K+ > Rb+ > NH+4 > Cs+ > Na+, whereas, by relative conductance in symmetric solutions, it is K+ > NH+4 > Rb+ > Cs+. In Cs+ solutions, single channel currents were too small to be measured directly, so nonstationary fluctuation analysis was used to determine the unitary Cs+ conductance. The single channel conductance displays an anomalous molefraction effect in symmetric mixtures of K+ and NH+4, suggesting that the conducting pore is occupied by multiple ions simultaneously.     

Abdominal Lipomatosis with Secondary Self-Strangulation of Masses in an Adult Rhesus Macaque (Macaca mulatta)

An 10-y-old, intact male rhesus macaque (Macaca mulatta) presented for bilateral scrotal swelling and a distended abdomen. A soft mass in the left upper quadrant of the abdomen was palpated. A barium study did not reveal any gastrointestinal abnormalities. Exploratory laparotomy revealed a large (1.25 kg, 15.0 × 13.0 × 9.5 cm), red and tan, soft, circumscribed, spherical mass within the greater omentum and 10 to 20 smaller (diameter, 1 to 4 cm), soft to firm masses in the mesentery and greater omentum. The resected mass was a self-strangulating abdominal lipoma, a pedunculated neoplasm composed of white adipocytes arising from peritoneal adipose tissue undergoing secondary coagulation necrosis after strangulation of the blood supply due to twisting of the mass around the peduncle. The smaller masses were histologically consistent with simple or self-strangulating pedunculated abdominal lipomas. The macaque presented again 9 mo later with a firm, 5.0-cm mass in the midabdomen, with intestinal displacement visible on radiographs. Given this animal''s medical history and questionable prognosis, euthanasia was elected. Necropsy revealed numerous, multifocal to coalescing, 1.0- to 15.0-cm, pale tan to yellow, circumscribed, soft to firm, spherical to ellipsoid, pedunculated masses that were scattered throughout the mesentery, greater omentum, lesser omentum, and serosal surfaces of the gastrointestinal tract. All of the masses were pedunculated abdominal lipomas, and most demonstrated coagulation necrosis due to self-strangulation of the blood supply. To our knowledge, this report is the first to describe abdominal lipomatosis with secondary self-strangulation of masses in a rhesus macaque.Lipomas have been reported frequently in veterinary medicine as benign subcutaneous neoplasms in canines¹⁶ or as pedunculated peritoneal masses with the potential to cause intestinal strangulation in geriatric horses.⁶ Abdominal lipomatosis (multiple abdominal lipomas) in humans and dogs had been reported only rarely and have been accompanied by clinical signs of abdominal distention with or without secondary gastrointestinal complications.¹⁶ Lipomas of the skin of nonhuman primates have affected a patas monkey, an African green monkey, rhesus macaques, and chimpanzees. Lipomas within the peritoneal cavity have been diagnosed rarely in nonhuman primates. Reported cases include an omental lipoma in a mona monkey and an adrenal lipoma in a hamadryas baboon.¹⁴ Here we report the clinical signs, postmortem examination, and histopathologic features of abdominal lipomatosis in a rhesus macaque (Macaca mulatta).     

Fluctuating asymmetries and advertisement call variation in the cricket frog, Acris crepitans

We used an anuran acoustic communication system to test a predictionof the "fluctuating asymmetries/good genes" hypothesis thatfemales prefer more symmetric mates because symmetry indicatesgenetic quality. Mate preferences of female cricket frogs (Acriscrepitans) can be influenced by three call characters: dominantfrequency, numbers of pulses per call, and number of pulse groupsper call. We tested the hypothesis that these preferences resultin females preferring more symmetric males. We measured fluctuatingasymmetries of characters not involved with the communicationsystem (head and tibia), and those involved in signal production(laryngeal characters) and signal reception (aural characters).We determined whether the asymmetries in these characters wererelated to the three variables that enhance call attractiveness.Most of the multiple regression models showed no significantassociation between the fluctuating asymmetries of charactersand any of the calls. The regression of head and tibia fluctuatingasymmetry on pulse number was significant, but partial regressioncoefficients revealed that more pulses were associated witha more symmetric head length and a less symmetric tibia length.Our findings provide little or no support for the fluctuatingasymmetries/good genes hypothesis. We emphasize, however, thatthis hypothesis should not be abandoned based on negative resultsof a single study, but deserves further scrutiny.     

A symmetric two locus model with viability and fertility selection

A two locus deterministic population genetic model is analysed. One locus is under viability selection, the other under fertility selection with both forms of selection completely symmetric. It is shown that linkage equilibrium may occur at two different equilibrium points. For a two-locus polymorphism to be stable, it is necessary that the viability locus be overdominant but not necessary that the fertility locus, considered separately, be able to support a stable polymorphism. The overlaps in stability are not as complex as under two locus symmetric fertilities, but considerably more complex than with symmetric viabilities. Extensions of the analysis for the central linkage equilibrium point with multiple viability and fertility loci are indicated.Research supported in part by NIH grants GM 28106 and GM 10452     

Inbreeding depression due to overdominance in partially self-fertilizing plant populations

The effect of the rate of partial self-fertilization and viability selection on the magnitude of inbreeding depression was investigated for the overdominance genetic model. The influence of these factors was determined for populations with equilibrium genotypic frequencies. Inbreeding depression was measured as the normalized disadvantage in mean viability of selfed progeny as compared to outcrossed progeny. When caused by symmetric homozygous disadvantage at a single locus it is shown always to be less than one-third. Moreover, for fixed rates of self-fertilization, its maximum value is found at intermediate levels of homozygous disadvantage. As the rate of self-fertilization increases, inbreeding depression increases and the homozygote viability that results in maximum depression tends toward one-half the heterozygote viability. Symmetric selection against homozygotes at multiple loci can lead to substantially higher values than selection at a single-locus. As the number of independent loci involved increases, inbreeding depression can reach high levels even though the selfing rate is low. Viability distributions for progenies produced from both random mating and self-fertilization were derived for the case of symmetric selection at independently assorting multiple loci. Distributions of viabilities in progenies resulting from mixtures of selfing and outcrossing were shown to be bimodal when inbreeding depression is high.     

Chronic spontaneous nephrocutaneous fistula associated with renal replacement lipomatosis

Chronic spontaneous nephrocutaneous fistula is a rare renal disease. Renal replacement lipomatosis (RRL) is the result of the atrophy and destruction of renal parenchyma with massive increases in the amount of fat in the sinus and perirenal space. The 2 conditions can be associated because they may have the same etiology. Indeed, urolithiasis is the most common cause of these diseases. We report a case of chronic nephrocutaneous fistula associated with RRL due to both urolithiasis and renal tuberculosis.     

Minimal nuclear pore complexes define FG repeat domains essential for transport

Translocation through nuclear pore complexes (NPCs) requires interactions between receptor-cargo complexes and phenylalanine-glycine (FG) repeats in multiple FG domain-containing NPC proteins (FG-Nups). We have systematically deleted the FG domains of 11 Saccharomyces cerevisiae FG-Nups in various combinations. All five asymmetrically localized FG domains deleted together were non-essential. However, specific combinations of symmetrically localized FG domains were essential. Over half the total mass of FG domains could be deleted without loss of viability or the NPC's normal permeability barrier. Significantly, symmetric deletions caused mild reductions in Kap95-Kap60-mediated import rates, but virtually abolished Kap104 import. These results suggest the existence of multiple translocation pathways.