Extracellular Enzyme Activities by Basidiobolus and Conidiobolus Isolates on Solid Media./Extrazelluläre Enzymaktivitäten bei Basidiobolus- und Condiobolus-Isólaten auf festen Medien

Summary: Fifty-seven isolates of Basidiobolus from reptiles and amphibians, and 7 other obtained from the American Type Culture Collection (ATCC) in Maryland were studied for their extracellular enzyme activities on solid media. The Conidiobolus isolates studied included 4 recovered from Nigerian soil and additional 4 obtained from the ATCC All these isolates produced active extracellular lipase and protease and failed to exhibit amylase, deoxyribonuclease and ribonuclease activities. The significance of the findings is discussed.
Zusammenfassung: Fünfundsiebzig Basidiobolus-Isolate aus Reptilien und Amphibien und sieben weitere aus der American Type Culture Collection (ATCC) in Maryland wurden auf Aktivtäten extrazellulärer Enzyme auf festen Medien untersucht Die untersuchten Conidiobolus-Isolate schlossen vier aus nigerianischen Böden und vier weitere aus der ATCC ein. Alle Isolate zeigten extrazellulär Lipase- und Proteaseaktivität Amylase-, Desoxyribonuclease- und Ribonucleaseaktivität war jedoch nicht nachzuweisen. Die Bedeutung dieser Befunde wird diskutiert.     

Situational panic attacks. Behavioral, physiologic, and biochemical characterization

To investigate the pathophysiology of nonpharmacologically induced panic attacks, 18 drug-free agoraphobic patients and 13 matched healthy subjects underwent structured exposure to phobic situations. Heart rate, blood pressure, and plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG), cortisol, growth hormone, and prolactin levels were measured before, during, and after exposure. Fifteen patients experienced situational panic attacks during exposure. Panicking patients displayed significantly greater increases in heart rate but not blood pressure or plasma free MHPG or cortisol in comparison with the healthy subjects. Growth hormone and prolactin responses tended to be smaller in the patients. If brain noradrenergic hyperactivity occurs during situational panic attacks, it may be too brief or too restricted in regional localization to affect MHPG levels in plasma. Chronically recurrent attacks may cause an adaptation of neuroendocrine mechanisms activated by anxiety or stress.     

Subclavian vein repair in patients with an ipsilateral arteriovenous fistula

Management of subclavian vein occlusive disease in persons with an ipsilateral arteriovenous fistula can be challenging. From July 1991 to May 1993, nine patients underwent direct exploration and repair of an obstructed subclavian vein following medial claviculectomy. Eight patients had polytetrafluoroethylene (PTFE) grafts; one patient had a Brescia-Cimino fistula. Intractable arm edema was the major symptom in five of eight. The site of the occlusive disease ranged from the midsubclavian vein to the proximal innominate vein. Pathology varied from a focal occluding web to a long segment of intimai fibroplasia. Five veins were occluded; four were stenotic. Surgical procedures consisted of endovenectomy and vein patch (four), endovenectomy and PTFE patch (one), resection of a focal stricture with end-to-end anastomosis (two), resection with PTFE interposition (one), and end-to-end internal jugular to subclavian vein transposition (one). Postoperative contrast venograms revealed a patent subclavian vein in eight of eight patients. One patient died postoperatively from unrelated causes; two patients died with a functioning fistula 8 and 12 months, respectively, after surgery. Two grafts were removed for infection and one deteriorated graft was abandoned because of repeated thrombosis. Only three of nine original grafts are currently in use, including one in which the ipsilateral subclavian vein rethrombosed. Although stent placement may now be the preferred treatment for subclavian vein stenosis, vein repair may still have a role in the treatment of subclavian vein occlusion, particularly in patients with a Brescia-Cimino fistula.Presented at the Twelfth Annual Meeting of the Southern California Vascular Surgical Society, Coronado, Calif., September 17–19, 1993.     

Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation,Which Associates With Body Composition in the Offspring

Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring. Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the Treatment of Obese Pregnant women (TOP)-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus control subjects (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus control subjects (false discovery rate [FDR] <5%) when using the Houseman reference-free method to correct for cell composition, and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms, including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared with control subjects. Methylation at 17 sites, annotated to, for example, DISC1, GBX2, HERC2, and HUWE1, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR <5%). Moreover, 22 methylation sites were associated with offspring BMI z scores during the first 3 years of life (P < 0.05). Overall, lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring’s lean mass and early growth.     

Structural studies offer a framework for understanding the role of properdin in the alternative pathway and beyond

Structures of alternative pathway proteins have offered a comprehensive structural basis for understanding the molecular mechanisms governing activation and regulation of the amplification pathway of the complement cascade. Although properdin (FP) is required in vivo to sustain a functional alternative pathway, structural studies have been lagging behind due to the extended structure and polydisperse nature of FP. We review recent progress with respect to structure determination of FP and its proconvertase/convertase complexes. These structures identify in detail regions in C3b, factor B and FP involved in their mutual interactions. Structures of FP oligomers obtained by integrative studies have shed light on how FP activity depends on its oligomerization state. The accumulated structural knowledge allows us to rationalize the effect of point mutations causing FP deficiency. The structural basis for FP inhibition by the tick CirpA proteins is reviewed and the potential of alphafold2 predictions for understanding the interaction of FP with other tick proteins and the NKp46 receptor on host immune cells is discussed. The accumulated structural knowledge forms a comprehensive basis for understanding molecular interactions involving FP, pathological conditions arising from low levels of FP, and the molecular strategies used by ticks to suppress the alternative pathway.     

Hypertension in the elderly: Age- and disease-related complications and therapeutic implications

Summary Effective treatment of hypertension in the elderly requires an understanding of both the progressive course of the disease and the impact of aging on the cardiovascular system, including physiological, genetic, lifestyle, and environmental factors. Review of the literature that has attempted to define the impact of an aging process on cardiovascular structure and function reveals a diversity of findings and interpretations. However, in general, normotensive elderly subjects exhibit the heart and vascular characteristics of muted hypertension, including many features of younger hypertensive patients: cardiac hypertrophy, diminution in resting left ventricular early diastolic filling rate, increased arterial stiffness and aortic impedance, diminution in the baroreceptor reflex, a diminished response to catecholamines and diminished renal blood flow, and an increase in peripheral vascular resistance (PVR). Treatment of elderly hypertensives is more challenging because of the greater likelihood of the presence of concomitant diseases, most importantly, coronary and peripheral atherosclerosis, renal dysfunction, and diabetes mellitus. Isolated systolic hypertension (ISH), the most common form of hypertension in the elderly, has also been clearly shown to be an important predictor of cardiovascular morbidity and mortality, including coronary artery disease, congestive heart failure, and stroke. Treatment of ISH has been shown to lower systolic pressure safely and effectively in the elderly. By reducing PVR, and possibly the arterial stiffness, and thus the early reflected pulse waves, vasodilators, including calcium antagonists, may lower these three components of arterial impedance, and hence lower the arterial load on the heart. The cardiac hypertrophy and reduced left ventricular filling rate associated with hypertension in older individuals can also be ameliorated, to some extent, by calcium channel blockers.Proceedings of a symposium held in Atlanta, Georgia on March 2, 1991.     

Assessment of the involvement of the macrophage migration inhibitory factor–glucocorticoid regulatory dyad in the expression of matrix metalloproteinase‐2 during periodontitis

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and counter‐regulator of endogenous glucocorticoids (GCs). It is implicated in acute and chronic inflammatory diseases. This study investigated the role of the MIF–GC regulatory dyad in the expression and release of matrix metalloproteinase‐2 (MMP‐2) during periodontitis, in vivo and in vitro. In a Mif‐knockout (KO) mouse model of ligature‐induced periodontitis, gingival tissues and blood were collected and analysed for levels of interleukin‐6 (IL‐6), MIF, MMP‐2, and corticosterone. In addition, human gingival fibroblasts (HGFs) were tested for production of IL‐6 and MMP‐2 after stimulation with hydrocortisone (HC), MIF, tumour necrosis factor‐alpha (TNF‐α), or Fusobacterium nucleatum, a pathogen known to elicit immune responses during periodontitis. Wild‐type (WT) mice showed a local and systemic increase of MIF levels during inflammation, which was confirmed by increased local IL‐6 concentrations. Systemic GC levels were reduced in WT and Mif‐KO mice during inflammation, with overall lower concentrations in Mif‐KO mice. In vivo and in vitro, MMP‐2 production was not dependent on MIF or inflammatory stimuli, but was inhibited by HC. Therefore, MIF does not appear to stimulate expression of MMP‐2 in the gingival tissues, whereas GC upregulates MIF and downregulates MMP‐2. Our findings further suggest that MIF may regulate systemic GC levels.