VS38: a new monoclonal antibody for detecting plasma cell differentiation in routine sections.

AIMS--To characterise a new mouse monoclonal antibody, VS38, which recognises an intracytoplasmic antigen of 64 kilodaltons present in normal and neoplastic plasma cells; and to establish its value as a diagnostic reagent for routine pathological practice. METHODS--A range of normal and neoplastic tissue sections, both frozen and routinely fixed, were immunostained, using the microwave method of antigen retrieval for routinely fixed specimens. The antibody was also tested on blood and bone marrow specimens and a range of human cell lines. The molecular weight of the antigen recognised by the antibody was obtained by western blot analysis. FACS analysis was used to demonstrate the cellular location of the antigen and its presence on tonsil cell suspensions and myeloma cases. RESULTS--VS38 recognised normal and neoplastic plasma cells in all of the tissues, including all routinely fixed plasma cell neoplasms tested. The antibody also weakly stained epithelial elements within the tissue but was absent from haemopoietic cells of other lineages. CONCLUSION--Antibody VS38 is of potential value in identifying myeloma or plasmacytoma in bone marrow or other tissues. It differentiates lymphoplasmacytoid lymphoma from lymphocytic and follicular lymphoma. It also subdivides large cell lymphomas into two groups which may be a more reliable method of separating these tumours than morphology alone.     

X-Ray Study of the Cat Hindlimb During Treadmill Locomotion

With pulsed X-ray cinematography we have analysed the angular excursions of the distal hindlimb joints (proximal interphalangeal, PIP; metatarsophalangeal, MTP; ankle) in cats walking on a treadmill. These distal joints transmit the body weight and the dynamic forces onto the ground. We have included the knee and hip joints in the analysis to relate the angular excursions of the proximal and distal joints and to verify the data previously obtained with external markers on the kinematics of the proximal joints. At the beginning of the stance phase the PIP joints flexed rapidly, the MTP joints extended slowly and the ankle and knee yielded under body weight. Whereas the PIP joints maintained a rather constant angular position of −75° throughout the stance phase, extension continued in the MTP joints from −230° at touch-down to −270° at the end of the stance phase. Around 50 ms before lift-off the MTP joints flexed rapidly. Early (−30 ms) after lift-off this flexion changed into a slow extension. The PIP joints extended swiftly at the stance-swing transition and moderately at the end of the swing phase. During the middle part of the swing phase they flexed slowly. Small rotatory movements around the long axis of the foot took place in the last 100 ms of the swing phase. The results of this study on the distal joints are discussed in relation to the placing of the paw, to the translation of forward propulsion into a MTP movement and to the lifting of the paw (conventionally described as toe curling). They show a differentiated mechanical interaction between the different distal limb joints during these different phases, which must be known in detail to interpret the corresponding electromyographic data and to understand how the hip is moved forward over the MTP joints which serve as the final pivot during stance.     

Overexpression of parathyroid hormone-related protein in the skin of transgenic mice interferes with hair follicle development.

Parathyroid hormone-related peptide (PTHrP) was initially discovered as the cause of the syndrome of humoral hypercalcemia of malignancy. Subsequently, the PTHrP gene has been shown to be expressed in a wide variety of normal tissues, including skin. Because the biological function of PTHrP in skin remains unknown, we used the human keratin 14 promoter to target overexpression of PTHrP to the skin of transgenic mice. We achieved a 10-fold level of overexpression in skin, and human keratin 14 promoter-PTHrP transgenic mice displayed a disturbance in normal hair follicle development. These mice either failed to initiate follicle development or showed a delay in the initiation of follicles. These findings suggest that PTHrP normally plays a role in the early stages of hair follicle development and support previous speculation that the peptide may function in regulating cellular differentiation.     

Nasal masks for domiciliary positive pressure ventilation: patient usage and complications.

BACKGROUND--Nasal mask discomfort is a major factor in compliance with treatment by nasal intermittent positive pressure ventilation (NIPPV) and nasal continuous positive airway pressure (CPAP). METHODS--A study of skin complications resulting from mask usage, with particular reference to predisposing factors, was carried out in 66 patients by means of a postal questionnaire. An effective means of managing ulceration at the nasal bridge while continuing therapy is described. RESULTS--Some disruption of treatment due solely to mask discomfort was experienced by 35 patients (53%), consisting of broken skin or open sores in 11 cases (17%). CONCLUSIONS-Although complications resulting from nasal mask usage are common, early identification of patients at risk of developing such complications and appropriate intervention will result in improved patient compliance.     

Cloning of a cDNA for the FAD-linked glycerol-3-phosphate dehydrogenase from rat liver and its regulation by thyroid hormones.

A full-length 2.4-kb cDNA for the FAD-linked glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) was cloned from rat liver using PCR techniques. The cloned gene encodes a protein of 727 amino acids. The calculated molecular mass of 80,898 Da is higher than the apparent molecular mass observed by SDS/PAGE (74,000 Da) of the purified enzyme. This result indicates that the enzyme is synthesized as a precursor with a putative mitochondrial signal sequence. mRNA for this gene was detected in liver, heart, muscle, brain, testes, and pancreas. With the exception of testes, basal expression levels were very low in all tissues examined. However, application of thyroid hormones led to a 10- to 15-fold increase in liver glycerol-3-phosphate dehydrogenase mRNA, whereas hypothyroidism further decreased the mRNA level.     

Bombesin improves survival from methotrexate-induced enterocolitis.

OBJECTIVE: The authors determined whether bombesin could improve survival from methotrexate (MTX)-induced enterocolitis. SUMMARY BACKGROUND DATA: Bombesin prevents gut mucosal atrophy, which is produced by feeding rats an elemental diet. Administration of MTX produces a lethal enterocolitis in rats fed an elemental diet. METHODS: On treatment day 0, 60 rats were divided randomly into three groups and fed an elemental diet (Vivonex TEN, Sandoz, Minneapolis, MN) as the only source of nutrition. Groups were subdivided further to receive either saline or bombesin (10 micrograms/kg, subcutaneously, three times a day) beginning either on day 0 or day 14. Methotrexate (20 mg/kg, intraperitoneally) was given to all rats 14 days after the start of an elemental diet. RESULTS: Bombesin prevented the mucosal atrophy in the ileum produced by the elemental diet and significantly decreased mortality in rats given MTX (whether given as a pretreatment or at the time of MTX administration). CONCLUSION: Bombesin significantly improved survival in a lethal model of MTX-induced enterocolitis, possibly by maintaining gut mucosal structure. Administration of bombesin to patients receiving chemotherapy may be clinically useful in preventing the severe enterocolitis induced by various chemotherapeutic agents.     

Precise and limited decompression for lumbar spinal stenosis

Summary Fifty-eight consecutive patients with lumbosacral nerve root entrapment due to spinal stenosis were treated with modified microsurgical decompression. Only the clinically relevant sides and levels were decompressed while the spinous processes, the interspinous ligaments, the medial portion of ligamentum flavum and the functionally important parts of the facet joints were preserved. The reviewers rated recovery as good or excellent in 71% of patients while patient self-assessment indicated 76% good or excellent outcome. These data suggest that microsurgical decompression of spondyloarthritic changes can effectively relieve the signs and symptoms of nerve root compression and that with careful evaluation of all available data the number of nerve roots requiring decomperession is often fewer than what is suggested by diagnositic images alone.     

Different postnatal development of cells expressing mRNA encoding neurotensin receptor.

In situ hybridization histochemistry revealed three different ontogenetic patterns of localized expression of the high-affinity type of neurotensin receptor mRNA in the developing rat brain: one comprises sites which showed transient expression of neurotensin receptor mRNA during the first postnatal week, the expression greatly decreasing thereafter (type I); another comprises sites at which there is a gradual increase in neurotensin receptor mRNA after birth, as there is in cell number and intensity, with advancing age, followed by a plateau (type II); the third comprises sites at which there is much expression of neurotensin receptor mRNA already at birth, and a slight decrease thereafter (type III). The cerebral cortex, except retrosplenial and entorhinal cortices, and the anterior dorsal thalamic nucleus exhibit the type I pattern, while the horizontal and vertical limbs of the diagonal band of Broca, magnocellular preoptic nucleus, substantia innominata, ventral part of the suprachiasmatic nucleus, medial habenular nucleus, ventral tegmental area and substantia nigra pars compacta exhibit the type II pattern. The tenia tecta, retrosplenial and entorhinal cortices exhibit the type III pattern. One of the most striking findings in this study was that the entire neocortex and most of the limbic cortex exhibit the type I pattern, i.e. neurotensin receptor mRNA is expressed transiently long before a neuronal network is established there. This suggests that neurotensin plays an important role in cortical development, other than its reported transmitter-like role in the adult.     

Combined anti-bradycardia/anti-tachycardia pacemaker-cardioverter-defibrillator systems in patients with recurrent ventricular tachyarrhythmias]

In 41 patients with recurrent sustained ventricular tachycardia and/or ventricular fibrillation an integrated pacemaker-defibrillator-system (PCD, Medtronic, model 7216 A or 7217 B) was implanted. In 21 out of 24 (88%) patients a new transvenous implantation technique in combination with a subcutaneous patch electrode was used. The implanted devices comprise antibradycardiac pacemaker functions, two different forms of antitachycardiac pacemaker functions (ramp and burst pacing), and internal cardioversion or defibrillation capabilities. During a mean follow-up of 8 months 147 episodes of ventricular tachycardia were detected, 131 of them were terminated successfully by antitachycardiac pacing; in 13 episodes internal cardioversion was applied to revert ventricular tachycardia. Twenty-seven episodes of ventricular fibrillation or rapid ventricular tachycardia (greater than 200/min) were detected and successfully terminated by internal defibrillation. In six patients with intermittent rapid atrial fibrillation, change of antiarrhythmic therapy was required to avoid activation of the device. The new integrated pacemaker-defibrillator systems improve therapy in patients with life-threatening tachyarrhythmias by reducing the number of internal cardioversions/defibrillations; the non-thoracotomy approach reduces the post operative risk.