Recessive, sex-Iinked, progressive, oculocerebral degeneration

Norrie's disease is a rare condition with a recessive sex-linked mode of inheritance, blindness with progressive ocular degeneration, and mental retardation of varying severity. Deafness and epilepsy may occasionally occur.
The findings in a 42-year-old, male. mentally retarded patient suffering from Norrie's disease are reported. His family tree is noted and the differential diagnosis of this condition is discussed.     

High-sensitivity, high-linearity, low-leak, self-balanced impedance cardiograph

An impedance cardiograph (so-called cardioimpedance meter) with the following characteristics is described: preadjustable current generator range of 0-4 mA rms at 100 kHz, crystal-controlled; sensitivity up to 50 V/omega with a resolution of 2 m omega; maximum nonlinearity of 2%; 0.7 microA arms of maximum leak current at 50 Hz; flat frequency response between 0 and 19 Hz. The instrument is self-balanced, using Arenson's bridge [1] with minor modifications, and is also able to operate as a plethysmograph, respirograph, and as an intracardiac Z-meter. Preliminary test as an impedance cardiograph yielded a correlation coefficient better than 0.8 when the stroke volume was evaluated by Kubicek's method and compared with values obtained using thermodilution.     

Recessive, sex-I inked, progressive, oculocerebral degeneration

Norrie's disease is a rare condition with a recessive sex-linked mode of inheritance, blindness with progressive ocular degeneration, and mental retardation of varying severity. Deafness and epilepsy may occasionally occur.
The findings in a 42-year-old, male, mentally retarded patient suffering from Norrie's disease are reported. His family tree is noted and the differential diagnosis of this condition is discussed.     

American Associatin of Anatomists. Eighty Sixth Annual Session,Cornell University Medical College,New York,New York,April 9, 10, 11, 12, 1973. Officers,abstracts, demonstrations

A method for producing flexible silicone rubber casts of the airways of the lungs in-situ is described. Casts are made to correspond to lung volumes occurring during normal breathing. The lung is prepared for casting by replacing the air within with CO₂ followed by filling with degassed physiological saline. The saline dissolves the CO₂ gas within the airways allowing for a bubble-free finished cast. Casting compound is then slowly injected through the trachea. The saline diffuses out of the lung and passes out of the thorax through several small slits in the thoracic wall. After the injection is completed, the cast lung is allowed to cure in-situ before it is removed and the tissue digested away. Finished casts have an overall shape corresponding closely to the shape of the thorax. Casts produced by this in-situ method appear to have more realistic geometrical relationships than those produced from excised lungs.     

Neocortical areas, layers, connections, and gene expression

Cortical patterns of gene expression provide a new approach to long standing issues of lamination, and area identity and formation. In this review, we summarize recent findings where molecular biological techniques have revealed a small number of area-specific genes in the nonhuman primate cortex. One of these (occ1) is strongly expressed in primary visual cortex and is associated with thalamocortical connections. Another gene, RBP, is more strongly expressed in association areas. It is not clear whether RBP might be linked with any particular connectional system, but several possibilities are raised. We also discuss possible roles of area-specific genes in postnatal development, and conclude with a brief sketch of future directions.     

Mesangial fenestrations, sieving, filtration, and flow

Small tracers in the circulation enter the rat mesangium rapidly and in large amounts that indicate a sizable plasma flow into the mesangium. Entrance is effected through mesangial fenestrations with a mean width in scanning electron microscopy of 376 A, a size similar to fenestrations in peripheral glomerular capillary walls. This is considerably smaller than the mean size of 678 A found with transmission electron microscopy, but the difference is probably due largely to the anionic surface coat on endothelial cells. Measurements of asymmetric thorium dioxide particles show that smaller ones with a mean length of 315 A enter the mesangium preferentially and that larger particles with a mean length of 405 A are partially restricted, supporting the idea that the measured width in scanning electron microscopy is close to the actual width in vivo. Fluid flow into the mesangium requires fluid flow out. The appearance time and accumulation of tracers suggest the following exit paths of flow from the mesangium: through the overlying epithelium into the urinary space contributing to glomerular filtration and concentrating large tracers beneath the basement membrane in the paramesangial region, into the efferent glomerular capillaries after tracers have been filtered out by the fibrillar matrix, and through the hilus into the juxtaglomerular apparatus (quantitatively small).     

Small cell carcinoma of the urinary bladder--histogenesis, genetics, diagnosis, biomarkers, treatment, and prognosis.

Small cell carcinoma of the urinary bladder is a rare but highly aggressive malignancy with a dismal prognosis. Most patients present with advanced disease at the time of diagnosis. Hematuria is the most frequent presenting symptom. Histologically, small cell carcinoma of the urinary bladder is indistinguishable from its pulmonary counterpart. Coexistence with other types of carcinoma is common. Histogenesis is uncertain; there are several competing theories, including origin from stem cells, from urothelial cells, and from neuroendocrine cells in normal or metaplastic urothelium. The molecular pathogenesis remains unclear. Immunohistochemical staining can be extremely helpful in establishing the diagnosis, and in investigating the use of potential therapeutic strategies. Currently, combinations of surgical resection, chemotherapy, and radiation therapy represent the main treatment options. The recent observation of c-kit and epidermal growth factor receptor expression in more than 25% of patients with urinary bladder small cell carcinoma opens new avenues for further investigation. Improvement in survival may depend upon the identification of new molecular markers to facilitate earlier diagnosis and the development of novel targeted therapies. In this paper, we review general aspects of small cell carcinoma of the urinary bladder, focusing on the ways in which our understanding of this entity has been positively influenced by studies of the histopathologic and immunohistochemical findings, and by investigations of genetic alterations in this disease.     

Frataxin, iron-sulfur clusters, heme, ROS, and aging

A deficiency in mitochondrial frataxin causes an increased generation of mitochondrial reactive oxygen species (ROS), which may contribute to the cell degenerative features of Friedreich's ataxia. In this work the authors demonstrate mitochondrial iron-sulfur cluster (ISC) defects and mitochondrial heme defects, and suggest how both may contribute to increased mitochondrial ROS in lymphoblasts from human patients. Mutant cells are deficient in the ISC-requiring mitochondrial enzymes aconitase and succinate dehydrogenase, but not in the non-ISC mitochondrial enzyme citrate synthase; also, the mitochondrial iron-sulfur scaffold protein IscU2 co-immunoprecipitates with frataxin in vivo. Presumably as a consequence of the iron-sulfur cluster defect, cytochrome c heme is deficient in mutants, as well as heme-dependent Complex IV. Mitochondrial superoxide is elevated in mutants, which may be a consequence of cytochrome c deficiency. Hydrogen peroxide, glutathione peroxidase activity, and oxidized glutathione (GSSG) are each elevated in mutants, consistent with activation of the glutathione peroxidase pathway. Mutant status blunted the effects of Complex III and IV inhibitors, but not a Complex I inhibitor, on superoxide production. This suggests that heme defects late in the electron transport chain of mutants are responsible for increased mutant superoxide. The impact of ISC and heme defects on ROS production with age are discussed.     

Behavioral phenotype of sex chromosome aneuploidies: 48,XXYY, 48,XXXY, and 49,XXXXY

Sex chromosomal aneuploidy is the most common disorder of sex chromosomes in humans, with an incidence of 1 in 400 newborns. The addition of more than one extra X and/or Y chromosome to a normal male karyotype is less frequent and has its own distinctive physical and behavioral profile. This study examines the behavioral similarities and differences in individuals with 48,XXYY compared to 48,XXXY and 49,XXXXY. The participants include 11 males with 48,XXYY and 13 males with 48,XXXY and 49,XXXXY. Using the Vineland Adaptive Behavior, the Achenbach Child Behavior Checklist, and the Reiss Personality Profiles, parents are asked to characterize the behavior and personality of their boys with sex chromosome tetrasomy and pentasomy. Males with 48,XXYY have higher overall adaptive scales in daily living skills, socialization, and communication compared to males with 48,XXXY and 49,XXXXY. Both groups are at risk for maladaptive behavior, although 48,XXYY males are at a higher risk for internalizing and externalizing symptoms. 48,XXXY and 49,XXXXY function at a lower cognitive level and their behavior is often immature for their chronological age. Both groups display interests in helping others, but have a low tolerance for being rejected or teased. Specific recommendations and interventional strategies are provided for individuals with 48,XXYY, 48,XXXY, and 49,XXXXY.     

2nd conference on heart, rheumatism and autoimmunity, Pescara, Italy, May 19-20, 2005

Systemic autoimmune diseases, which comprise a family of conditions which share common pathogenetic mechanisms, are frequently associated to cardiac involvement and to a high prevalence of ischemic coronary events often occurring at a younger age than in normal population. A large increase in mortality is related to premature atherosclerosis with coronary artery disease and stroke in patients with connective tissue diseases. Coronary heart disease is responsible for 40-50% of the death of patients with rheumatoid arthritis. Moreover, a growing body of evidence supports the view that autoimmune mechanisms are involved in the pathogenesis of cardiovascular disease. Inflammatory heart disease is a rising concern worldwide. Similar mechanisms link autoimmune diseases, including the association of increased disease with proinflammatory cytokines and the importance of regulatory mechanisms in the control of chronic inflammation. The role of the immune system in modulating atherosclerosis has recently been well documented. Studies have revealed that cellular and humoral immunity plays crucial roles in atherogenic plaque formation. This includes macrophages, CD4+ T cells and dendritic cells as well as autoantigens such as oxidized low-density lipoprotein (oxLDL), heat shock proteins and beta2-glycoprotein I. The inflammatory component is not localized to the "culprit" plaque, but it is diffused to the entire coronary vascular bed, and involves also the myocardium. The aim of the conference (2nd conference on heart, rheumatism and autoimmunity) was to focus the attention of the participants on some pathogenetic, clinical and therapeutic aspects at the boundary between cardiology and rheumatology and to encourage the debate among clinicians and basic researchers with different backgrounds and experiences.     

Learning,habituation, and training

Summary The apparent efficiency of sub-maximum exercise tends to be lower in subjects with a large aerobic power. This is probably an artefact arising from neglect of the oxygen debt in the calculation of mechanical efficiency. Changes in the extent of oxygen debt can obscure an increased skill of performance with training. Efficiency is improved by repetition of a given mode of exercise, but not by other forms of training. Habituation is greater during work than at rest, but even during work the change in pulse rate of young men does not exceed 2–5 beats/min over 5 experimental days. Habituation is lost if the test procedure is not repeated during training; this can complicate assessments of training from the response to sub-maximum exercise.     

Nouns, verbs, objects, actions, and the animate/inanimate effect

We report an aphasic patient, Z.B.L., who showed a significant advantage for verbs compared to nouns in picture-naming tests. Within the object class, he performed better on animate things than on nonliving things in picture naming as well as in an "attribute judgement task". This pattern of performance is contrary to the central prediction of a recent proposal (Bird, Howard, & Franklin, 2000), which attributes noun-verb dissociation in aphasic patients to deficits in processing certain kinds of semantic features. This model proposes that conceptual representations of verbs have a lower proportion of sensory features than do representations of nouns; the same is proposed for inanimate versus animate items within the noun category. Noun deficits are assumed to arise due to impairment for the processing of sensory features. The model predicts that if a patient is more impaired for nouns than for verbs, he will also display more difficulty with animate than with inanimate objects. Contrary to predications derived from this theory, Z.B.L. performed better with animate than inanimate nouns.     

IgA, IgG, IgM, and IgE levels in normal, healthy, non-atopic Israeli children

IgA, IgG, IgM, and IgE levels in healthy, non-atopic, Israeli-born children aged 20 days to 16 years were analyzed and showed similar age-related values and dynamics as those of white populations found in other countries. No significant effect of sex of the individual or ethnic origin of the parents was found on the IgE values at different ages. This may indicate that total IgE levels are strongly influenced by environmental factors. Establishing tolerance limits at 97.5, 95, 75, 25 and 5th percentiles and the geometric mean provides the practitioner with more complete reference values. The use of multivariate control charts with tolerance limits from normal IgA, IgG, IgM, and IgE levels is described and is offered as an additional tool for the diagnosis of an allergic individual.     

Hydrocephalus, agyria, pseudoencephalocele, retinal dysplasia, and anterior chamber anomalies.

An infant presenting with hydrocephalus, pseudoencephalocele, agyria, and ocular defects, consisting of anterior chamber anomalies and retinal dysplasia, is reported. This is thought to be a further case of an autosomal recessive syndrome of which six cases have been previously described.     

Relationships between human thirst, hunger, drinking, and feeding

There is a widely held view that hunger prompts feeding to ensure energy needs are met, while thirst cues drinking to address hydration requirements. However, recent changes in the nature of the food supply and eating patterns have raised questions about the functionality of these relationships with respect to maintaining energy balance. The increasing consumption of energy-yielding beverages and foods with diluted energy density, through the use of ingredients such as high-intensity sweeteners and fat replacers, poses new challenges to presumed homeostatic energy regulatory mechanisms. This review draws on findings from a recent observational study and other published evidence to explore whether shifts of food composition and use patterns may be disrupting relationships between thirst, hunger, drinking, and eating, resulting in positive energy balance (e.g., drinking low satiety, energy-yielding beverages in response to hunger). The observational study entailed collecting hourly appetitive ratings and dietary recalls from 50 adults for seven consecutive days. These data reveal a clear bimodal daily hunger pattern, whereas thirst is stronger and more stable throughout the day. Further, approximately 75% of fluid intake occurs peri-prandially, with the majority derived from energy-yielding beverages. While there is published evidence that drinking is responsive to feeding, support for the view that drinking is the more tightly regulated behavior is stronger. Our data indicates that, due to a number of plausible factors, neither absolute values nor changes of hunger or thirst are strong predictors of energy intake. However, it is proposed that stable, high thirst facilitates drinking, and with the increased availability and use of energy-yielding beverages that have low satiety properties, can promote positive energy balance. There are marked individual differences in mean daily hunger and thirst ratings with unknown implications for energy balance.     

An autosomal recessive ectodermal dysplasia syndrome of hypotrichosis,onychodysplasia, hyperkeratosis,kyphoscoliosis, cataract,and other manifestations

We describe a 20-year-old woman with generalized trichodysplasia, dry skin with scaling, hyperchromic spots on limbs, hyperkeratosis (particularly intense on soles), dermatoglyphic abnormalities, onychodysplasia, shortness of stature, kyphoscoliosis, unusual facial appearance, minor malformations of limbs, bilateral nuclear cataract, narrow palpebral fissures, entropion, trichiasis, etc. The condition is probably due to an autosomal recessive gene. The patient is the only affected member in a sibship of four whose parents are second cousins.     

Sporadic case of warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis syndrome

The term WHIM syndrome (WHIMS) is an acronym describing a rare primary immunodeficiency disorder characterized by warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis, the unusual association of neutropenia with bone marrow myeloid hypercellularity. WHIMS was recently associated with mutations in the gene encoding the chemokine receptor CXCR4 and as such is the first disease ascribed to abnormalities of chemokine signaling. We report a sporadic case of WHIMS in a woman presenting with recurrent infections and human papilloma virus-related genital dysplasia.     

Syndromes of microcephaly, microphthalmia, cataracts, and joint contractures

Three infants are described, one with the Neu-Laxova syndrome and two with the cerebro-oculo-facio-skeletal (COFS) syndrome. The relationship between these two syndromes is discussed in the light of the present cases and others in published reports.     

Some general pathological and biological categories: health, disease, homeostasis, sanogenesis, adaptation, immunity. New approaches and definitions

The article outlines new approaches to definition of categories of homeostasis, health, disease and sanogenesis in terms of relationships between human body and environment. According to these definitions, health is the state of the body with unaffected functional dynamic homeostasis securing optimal functioning for productive relations with the environment; disease is the state of the body with affected functional dynamic homeostasis and its inability to accomplish functions for productive relations with the environment. These formulations reflect biological and social aspects of the above categories.