Sperm motility in the presence of boundaries

The fluid dynamics of sperm motility near both rigid and elastic walls is studied using the immersed boundary method. Simulations of both single and interacting organisms are presented. In particular, we find that nearby organisms originally undulating with a 90° phase shift may adjust their relative swimming velocities and phase-lock. Comparisons with previous analytical results are also discussed. The tendency of a near-wall to attract organisms is demonstrated.     

Regulation of insulin-like growth factor (IGF) binding protein-2 synthesis and degradation by platelet-derived growth factor and the IGFs is enhanced by serum deprivation in vascular smooth muscle cells

Growth factors such as platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF-1) stimulate proliferation and migration of vascular smooth muscle cells (SMC). IGF-l bioactivity is modulated by high-affinity binding proteins (IGFBP) which are important regulators of these processes. Procine vascular SMC synthesize IGFBP-2 and IGFBP-4 in vitro. In the present study, levels of IGFBP-2 in conditioned media (CM) were increased approximately 1.6 to 2.2-fold when cells were exposed to PDGF (20 ng.ml) or insulin (5 μg/ml) for 24 hr following a 24 hr incubation in serum-free media, or following a 72 hr exposure to either growth factor. Similar increases in IGFBP-2 mRNA levels were observed. Exposure of cells to PDGF for 24 hr without prior serum deprivation resulted in smaller (47 ± 11%) increases in IGFBP-2 protein levels but failed to alter mRNA levels. IGF-1, FGF-b? and EGF failed to increase IGFBP-2 using either experimental paradigm. In contrast, IGFBP-2 protein levels were consistently decreased (75 ± 14%) after 72 hr of exposure to IGF-II without corresponding decreases in IGFBP-2 mRNA levels. Immunoprecipitation of [³⁵S] methionine-labeled IGFBP-2 indicated that this decrease was not due to a decrease in synthesis of IGFBP-2. Immunoblot analysis of CM from cells treated with IGF-II indicated that the decrease in intact protein corresponded with an increase in two non-IGF binding IGFBP-2 fragments of 22 and 14 kD. Increased abundance of these fragements was also observed following IGF-I exposure, although corresponding decreases in intact IGFBP-2 were not usually observed. The relative abundance of these fragments did not appear to be affected by treatment with PDGF or insulin. In contrast to IGFBP-2, regulation of the levels of IGFBP-4 in CM did not appear to be altered by serum deprivation. Insulin consistently increased IGFBP-4 mRNA and protein levels under all situations. PDGF tended to increase IGFBP-4 protein levels, although this effect was less consistent and not as great as the increase observe with insulin. Treatment with IGF-I or -ll consistently decreased IGFBP-4 levels in CM but tended to increase their mRNA levels under all situations. These data indicate that insulin, PDGF, and the IGFs regulate both IGFBP-2 and IGFBP-4. While PDGF and insulin stimulate IGFBP-2 and 4 synthesis, the IGFs appear to activate protease(s) which regulate IGFBP-2 and -4 levels post-translationally. The regulation of IGFBP-2 levels by each of these mechanisms appears to be amplified by serum deprivation, but this is not observed with IGFBP-4. © 1995 Wiley-Liss, Inc.     

Two New Species of Aphelenchoididae (Nemata) from Declining Red Pines in Maryland

Aphelenchoides resinosi n. sp. and Ektaphelenchus joyceae n. sp. are described and illustrated from red pines of the Allegheny plateau of Maryland, USA. The new species were found in trees infested with Bursaphelenchus xylophilus. Primary diagnostic characters of A. resinosi females are constriction of the head, basal stylet knobs, tong postuterine sac, two incisures in the lateral field, and conical tail four to five anal body widths long with a simple terminal mucro. Diagnostic characters of the males are two pairs of subventral caudal papillae and spicule shape: Primary diagnostic characters of E. joyceae females are a slight constriction of the head, six similar lips, conical tail, and short postuterine sac. Diagnostic characters of the males are spicule size and shape, a single row of spermatocytes, and one pair of caudal papillae. Within-tree distributions of A. resinosi and E. joyceae are presented. A total of 70% of both red-needled and chlorotic-needled trees in the study were positive for A. resinosi and E. joyceae. Branch hierarchy was related to the percentage of samples positive for A. resinosi.     

XY gonadal dysgenesis and gonadoblastoma: a study in two sisters with a cryptic deletion of the Y chromosome involving the SRY gene

This paper reports a case of XY gonadal dysgenesis in two sisters. Both patients presented an eunochoid female phenotype with normal external genitalia. At laparotomy, the elder sister was found to have bilateral gonadoblastoma. Cytogenetic studies, which included G and C banding and in situ hybridization, showed that the patients had an apparently normal 46, XY karyotype. PCR analyses revealed absence of the conserved portion (HMG box) of the SRY gene and of the Y chromosome pseudoautosomal boundary region sequence in both patients. The presence of the ZFY sequence was detected by Southern hybridization in the two affected sisters. The patients' father (46, XY, no mosaicism detected in peripheral blood lymphocytes) was positive for SRY and ZFY sequences. The occurrence of gonadoblastoma is discussed in terms of the genetic factors that may lead to tumor development.     

Combined use of 13C chemical shift and 1Hα−13Cα heteronuclear NOE data in monitoring a protein NMR structure refinement

Summary A large portion of the ¹³C resonance assignments for murine epidermal growth factor (mEGF) at pH 3.1 and 28°C has been determined at natural isotope abundance. Sequence-specific ¹³C assignments are reported for 100% of the assignable C, 96% of the C, 86% of the aromatic and 70% of the remaining peripheral aliphatic resonances of mEGF. A good correlation was observed between experimental and back-calculated C chemical shifts for regions of regular -sheet structure. These assignments also provide the basis for interpreting ¹H–¹³C heteronuclear NOE (HNOE) values in mEGF at natural isotope abundance. Some of the backbone polypeptide segments with high internal mobility, indicated by these ¹H–¹³C HNOE measurements, correlate with locations of residues involved in the putative mEGF-receptor binding site. Using four families of mEGF structures obtained over the last few years, we demonstrate that standard deviations between experimental and back-calculated C values can be used to monitor the refinement of this protein's structure, particularly for -sheet regions. Improved agreement between calculated and observed values of C is correlated with other measures of structure quality, including lowered values of residual constraint violations and more negative values of conformational energy. These results support the view that experimental conformation-dependent chemical shifts, C, can provide a reliable source of information for monitoring the process of protein structure refinement and are potentially useful restraints for driving the refinement.Abbreviations HSQC heteronuclear single-quantum coherence spectroscopy - PFG pulsed-field gradient - TOCSY ¹H-¹H total correlation spectroscopy - EGF epidermal growth factor - mEGF murine EGF - hEGF human EGF - hTGF human type- transforming growth factor - DIPSI spm-locking pulse sequence - NOE nuclear Overhauser effect - HNOE heteronuclear Overhauser effect     

Ectopic ACTH syndrome

Ectopic ACTH syndrome represents a cancer-induced amplification of a property [proopiomelanocortin (POMC) peptides production] normally present in the cells from which the cancer originated but with aberrant posttranslational processing of POMC resulting in a greatly elevated secretion of ACTH precursors. The classic ectopic ACTH-producing tumors described in the 1960s were highly malignant but more recently slowly growing tumors such as carcinoids are reported with increasing frequency. Clinical features of patients with ectopic ACTH were analyzed, including biochemical abnormalities, plasma ACTH, cortisol and urinary steroids. Dynamic tests such as high-dose dexamethasone suppression, metyrapone and ovine-CRH (oCRH) stimulation were explored, as well as inferior petrosal sinus ACTH sampling before and after oCRH. Among the tumor markers examined, elevation of ACTH precursors was uniformly present followed by increased output of calcitonin, gut hormones, oncofetal and placental hormones in decreasing order. Since more than 90% of ectopic ACTH tumors are neuroendocrine in nature exhibiting APUD characteristics, their 2 markers, neuron-specific enolase and chromogranins are very useful. The imaging procedures for localization of the tumor ranged from chest X-rays to computed tomography and magnetic resonance of the chest and abdomen. Abdominal ultrasonography was also useful. Finally somatostatin receptor scintigraphy permitted demonstration of unrecognized tumors and/or metastases, even when the tumors were occult. The ACTH content, immunostaining for APUD markers and altered POMC processing were evaluated in ectopic tumors and/or metastases. Occult ectopic ACTH syndrome of more than 4–6 months of symptoms without the emergence of an obvious source was reviewed. Since the tumors are often clinically and biochemically undistinguishable from pituitary-dependent Cushing's disease, inferior petrosal sinus sampling for ACTH after oCRH stimulation established the diagnosis in over 90% of the cases. 60% of the occult tumors were thoracic carcinoids (3/4 bronchial carcinoids), followed by small cell lung cancer and pancreatic neuroendocrine tumors. In 12% the primary etiology was not detected. The rare syndrome of ectopic CRH syndrome (6 published cases) leading to excessive stimulation of the pituitary which became hyperplastic and secreted excessive amounts of ACTH is discussed. Finally, the 12 published cases and 1 unreported patient with ectopic CRH-ACTH tumors were reviewed, the majority being metastatic small cell lung carcinomas, bronchial and thymic carcinoids.     

FALSE ANEURYSM OF THE LEFT VENTRICLE: CASE REPORT WITH PRE- AND POSTOPERATIVE EVALUATION

A 66-year-old woman developed chronic congestive heart failure after myocardial infarction of the anterior wall of the left ventricle. Angiographic studies revealed total proximal occlusion of the left anterior descending coronary artery and a large saccular aneurysm located on the anteroapical aspect of the left ventricle. Resection of a false aneurysm at operation resulted in improved cardiac function, and the patient made an uneventful recovery. Repeat evaluation six months later confirmed normal cardiac hemodynamics and left ventricular angiographic characteristics. To our knowledge, this is the first documented case of normalized heart function resulting from resection of a false aneurysm of the left ventricle. Functional classification according to the New York Heart Association improved dramatically, rising from Class IV preoperatively to Class I after operation.     

Primitive nervous systems: Peripheral habituation in decerebrate polyclad flatworms

The response to a vibration stimulus recorded from the cords of the ventral submuscular plexus of the polyclad flatworm, Notoplana acticola, consists of a burst of action potentials. The response can be abolished by the application of MgCl₂ to the sea water bathing the preparation. With repeated application of the stimulus, decreasing numbers of action potentials can be measured. This waning responsiveness can be dishabituated by applying a more intense vibration stimulus or with electrical shocks applied directly to the ventral nerve plexus. With electrical stimuli a number of shocks have to be applied before the response can be dishabituated. Changes in responsiveness can be measured simultaneously in a number of sites in the plexus even after the nerves between recording sites have been severed. With different interstimulus intervals the extent of habituation changes. As interstimulus intervals increase from 1 to 5 sec, there appears to be a decrease in responsiveness which recovers when interstimulus intervals become longer than 5 sec.