Genetic Analyses of the Mouse Deafness Mutations Varitint-Waddler (Va) and Jerker (Espnje)

Genetic studies on spontaneous mouse mutants with hearing defects have provided important insights into the function of genes expressed in inner ear hair cells. Here we report on our genetic analyses of the deaf mutants varitint-waddler (Va) and jerker (Espnje). A high-resolution genetic map localizes VaJ to a 0.14 ± 0.08 cM region between D3Mit85 and D3Mit259 on distal chromosome 3. By comparative mapping, the human ortholog resides at 1p22.3 between markers D1S3449 and D1S2252. To study the effect of different genetic backgrounds on the hearing phenotype, Espnje and VaJ were crossed to various inbred strains. Auditory-evoked brainstem response tests on F2 progeny demonstrate that expression, inheritance, and penetrance of the hearing phenotype are solely controlled by the mutant allele. To test for a genetic interaction between Espnje and Cdh23v, auditory function was analyzed in double heterozygotes; no significant increases of thresholds of sound pressure levels were observed. The results establish the framework for cloning the Va gene and provide valuable insights into the genetics of deafness mutations in the mouse.     

Biology and Biomechanics in Osteosynthesis of Proximal Humerus Fractures

Abstract Surgical treatment of proximal humeral fractures still remains a challenge. This is primarily due to the fact that sufficient implant fixation in humeral head fractures is often not achieved due to substantial bone tissue loss with increasing age. In the last few years the locking plates and locking nails have been introduced into clinical practice with varying results. The biomechanical studies have focused on locking plate osteosynthesis as well. The following paper focuses on bone quality, biomechanical studies and biology of proper osteosynthesis and reviews the most recent literature.     

Verruciform xanthoma]

BACKGROUND: Verruciform xanthoma (VX), a rare, benign lesion of the skin and mucosa, is slow-growing, asymptomatic and characterized by a granular (verruciform) surface. It is yellowish-red or grey in color and up to 2 cm in diameter. Histologically, a papillary and/or verrucous proliferation of the squamous epithelium with hyperparakeratosis and numerous foam cells is present. These cells are predominantly located within the papillae of the lamina propria. For differential diagnosis, other papillomatous and verrucous lesions such as verrucous carcinomas or squamous cell carcinomas need to be ruled out. CASE REPORT: A 46-year-old patient with VX located on the alveolar process regio 26-28 is presented. Clinically, a 2 x 2 cm granular, oral mucosa surface lesion extending onto the palate occurred in regio 26-28. Biopsy was characterized light microscopically by the presence of swollen, elongated cells in the submucosa, an indication of VX alterations. Transmission electron microscopy demonstrated foam cells in the subepithelium containing numerous membrane-bound vesicles similar in diameter and showing a wide variation in electron density. Morphologically, these cells resembled macrophage-related cells. The lesion was excised in total with no evidence of recurrence after 9 months. DISCUSSION: The pathogenesis of VX is still unclear. The characteristic xanthoma cells may play a major role in VX. Microscopic analysis of the morphology of the foam cells indicated that they may represent a differentiated form of macrophages. Lipid vesicles inside these cells differed in their electron density indicating a heterogeneous biochemistry or different states of maturation.     

Physiologic and pathologic evaluation of chronic extra-aortic counterpulsation with latissimus dorsi flap. Preliminary results

This study attempted to evaluate the efficacy of chronic extra-aortic counterpulsation with a latissimus dorsi neuro vascular flap. Five dogs had a preliminary procedure consisting of the creation of a latissimus dorsi flap and a thoracotomy in which the flap was wrapped around the descending aorta just distal to the left subclavian artery. An epicardial lead was placed on the left ventricle and a nerve stimulating lead placed around the thoraco-dorsal nerve. Three weeks later, both leads were connected to a cardiomyostimulator programmed to function in a counterpulsation mode with a 1:2 assist frequency. Hemodynamic measurements were made at 6 and 8 and 10 and 12 weeks and the dogs were sacrificed. Three dogs had all sets of hemodynamic measurements made. Two of the three dogs demonstrated diastolic augmentation at 6 and 8 and 10 and 12 weeks average 20 to 25 mmHg. The third dog failed to demonstrate any change. All dogs were sacrificed at 12 weeks and specimens were submitted for histologic evaluation. The muscle flap was preserved in all animals. The aorta subjacent to the flap showed, (1) normal intima with no evidence of disruption or thrombus in all animals, (2) in the animals in whom counterpulsation was observed, there appeared to be thinning of the media in the aorta subjacent to the muscle flap, and (3) no evidence of distal emboli. This study demonstrated that chronic counterpulsation can be obtained with a latissimus dorsi flap. The actual hemodynamic benefits are not determined from this study. The medial thinning in the aortic wall may limit the long-term benefit of this procedure.     

Characteristics of deoxycholic acid-induced histamine release from mast cells of guinea-pig rectocolonic mucosa and rat peritoneal cavity

Deoxycholic acid (DA) caused a dose-related release of histamine (HR) from mast cells of rat peritoneum (RPMC) and mucosal cells of guinea pig rectocolon (RCMC). In both cell populations, DA-induced HR was: (1) accompared by a parallel release of lactate dehydrogenase (LDH), (2) not affected by metabolic inhibitors, (3) dependent on time of incubation, temperature and pH, and affected by Ca⁺⁺ concentration in RPMC but not in RCMC. DA-induced HR from RCMC may be involved in certain functional disorders of the colon.     

Expression of blood group-related carbohydrate antigens in normal human pancreatic tissue

The expression of type 1, 2 and 3 chain carbohydrate structures in 15 normal pancreata was investigated by immunohistochemical methods using well-defined monoclonal antibodies. Surgical biopsies of pancreata were obtained from kidney donors while the organs were still perfused. Type 1 chain structures were abundantly expressed including monosialylated(ms)- and disialylated(ds)-Le(a) antigens, which have previously been associated with cancer. Type 2 chain structures were represented by H and Le(y) antigens and to a lesser extent by the precursor structure N-acetyllactosamine, whereas Le(x), dimeric Le(x), and ms-Le(x) were only sporadically observed, in contrast to fetal pancreatic tissue, in which Le(x) has been found to be abundantly expressed. H chain 3 antigen was found in nearly all specimens, whereas precursor structures Tn, sial-Tn and T antigens were absent. Desialylation unmasked the T antigen in all specimens. Absence/masking of Tn, T and related antigens is of special interest, since these antigens are associated with tumor development in other tissues, and may be of importance in pancreatic cancer diagnostics in the future.     

Internal derangement of the temporomandibular joint: a histochemical study.

The purpose of this study was to correlate histologic findings in temporomandibular joint (TMJ) condyles and discs with their macroscopic appearance at surgery. The 24 patients with internal derangement of the joint included 20 women and 4 men (mean age, 37 years; range, 18 to 61 years). The tissue lesions varied in degree from mild soft-tissue fraying and bone remodeling to extensive resorption and new cartilage and bone formation with high phosphatase enzyme activities, and even to loss of articular soft tissue and breakdown of cortical bone. Reactions may arise in the hard tissues before they occur in the articular surface layers.