Bilateral, simultaneous, spontaneous rupture of quadriceps tendons without trauma in an obese patient: a case report.

This is a single case report of bilateral, simultaneous, spontaneous rupture of the quadriceps tendon caused by obesity without trauma. The patient was a 52-year-old, 350-pound, morbidly obese man with a sedentary life style whose quadriceps tendons ruptured while he was descending a staircase. He presented with a large deficit superior to the patella and an inability to straighten his knees. After surgery, his knees were immobilized in extension for 6 weeks, followed by gradual weight bearing and gait training with braces. He was weaned off the braces as he increased the range of motion and strength in his knees. The rehabilitation process was protracted, and he returned to full-time work 6 months postinjury. Physiatrists should be familiar with the diagnosis, treatment, and rehabilitation of this rare condition.

The postpericardiotomy syndrome as a cause of pleurisy in rehabilitation patients.

Pleuritic chest pain in patients on a rehabilitation unit may be caused by several conditions. We report 2 cases of postpericardiotomy syndrome (PPS) as a cause of pleuritic pain. PPS occurs in 10% to 40% of patients who have coronary bypass or valve replacement surgery. The syndrome is characterized by fever, chest pain, and a pericardial or pleural friction rub. Its etiology is believed to be viral or immunologic. The syndrome can be a diagnostic challenge, and an increase in length of hospitalization because of it has been documented. Identified risk factors for PPS include age, use of prednisone, and a history of pericarditis. A higher incidence has been reported from May through July. Many patients undergo a battery of expensive procedures before PPS is diagnosed. The pain is sharp, associated with deep inspiration, and changes with position. Pleural effusions may be present and tend to occur bilaterally. Pericardial effusions are a documented complication. A pericardial or pleural rub may be present and is often transient. Serial auscultation is important. Laboratory work provides clues with a mild leukocytosis and an elevated erythrocyte sedimentation rate. However, this does not provide the definitive diagnosis. Cardiac enzymes are not reliably related to the syndrome. An electrocardiogram will show changes similar to those associated with pericarditis. The patient may have a fever, but it is rarely higher than 102.5 degrees F. Complications include pericardial effusions, arrhythmias, premature bypass graft closure, and cardiac tamponade. Treatment consists of a 10-day course of nonsteroidal anti-inflammatory drugs.

Increasing confidence in vergence as a cue to distance.

Multiple cues contribute to the visual perception of an object's distance from the observer. The manner in which the nervous system combines these various cues is of considerable interest. Although it is accepted that image cues play a significant role in distance perception, controversy exists regarding the use of kinaesthetic information about the eyes' state of convergence. We used a perturbation technique to explore the contribution of vergence to visually based distance estimates as a function of both fixation distance and the availability of retinal information. Our results show that the nervous system increases the weighting given to vergence as (i) fixation distance becomes closer; and (ii) the available retinal image cues decrease. We also identified the presence of a strong contraction bias when distance cues were studied in isolation, but we argue that such biases do not suggest that vergence provides an ineffectual signal for near-space perception.

Transient expression of the neurofilament proteins NF-L and NF-M by Schwann cells is regulated by axonal contact.

Expression of the genes that encode neurofilament proteins is considered to be confined normally to neurons. However, in demyelinating peripheral nerves Schwann cells upregulate the mRNA for the medium-sized neurofilament protein (NF-M), and cultured Schwann cells of the myelin-forming phenotype can also synthesize and incorporate NF-M protein into their intermediate filament (IF) cytoskeleton. The purpose of this study was to establish how axonal contact might influence glial neurofilament gene expression and regulate the synthesis of neurofilament proteins. We show that the gene encoding NF-M is expressed at early stages of differentiation in myelin-forming Schwann cells in vivo; nevertheless, little NF-M protein can be detected in these cells. The transient induction of NF-M mRNA is also apparent in dedifferentiating Schwann cells during Wallerian degeneration. In these Schwann cells the mRNAs for NF-M and NF-L (the smallest polypeptide), but not NF-H (the largest neurofilament subunit), are coordinately expressed. In contrast to differentiating myelin-forming Schwann cells, the cells of degenerating nerves express both NF-M and NF-L polypeptides. Restoration of axonal contact in the growing nerve stimulates the recapitulation of Schwann cell differentiation including the elevation of NF-M and NF-L mRNA expression. These results demonstrate that the transient induction of neurofilament mRNAs in Schwann cells is a feature of both differentiation and dedifferentiation. However translation of these mRNAs is confined to Schwann cells deprived of axonal contact either by nerve injury or by culture in the absence of axons. These findings suggest that the expression of the NF-M and NF-L polypeptides is an important characteristic of those Schwann cells that will contribute to the repair of damaged peripheral nerves.

Specialist orthodontics in the General Dental Service.

This study investigated treatment times and treatment standards produced by 10 specialist orthodontic practitioners working in the General Dental Service (GDS) in England. Twenty cases from each practitioner, consecutively completed with two-arch fixed appliance therapy, were selected and assessed to evaluate treatment times and treatment standards. Observer-generated timings were recorded to provide values for the time taken by these practitioners to perform the various component activities associated with fixed appliance orthodontic therapy. These timings were then pooled to produce an 'average' value for each procedure. Treatment time was assessed retrospectively by applying these average times to the appropriate appointments, as documented on the patient's record card. The treatment duration, number of visits, appliance type and extraction regime were also recorded. Treatment standards were assessed by applying the weighted Peer Assessment Rating Index (PAR Index) to pre- and post-treatment study casts. Relationships between each of these variables were investigated using multiple regression analysis. No relationship was found between treatment time and PAR score change. Predictors of treatment time were the number of visits, and more interestingly, the use of extra-oral forces. However, no useful predictors of the treatment standard were found. On the basis of this sample, it appears that when specialist orthodontic practitioners in the GDS provide two-arch fixed appliance therapy: treatment is completed, on average, in 3-5 hours of chairside time, in 20 visits, spread over 22 months; they provide a high standard of treatment, as assessed by the PAR Index, to a caseload of patients in need to treatment.

Schwann cells of the myelin-forming phenotype express neurofilament protein NF-M.

Immature Schwann cells of the rat sciatic nerve can differentiate into myelin-forming or non-myelin-forming cells. The factors that influence this divergent development are unknown but certain markers such as galactocerebroside distinguish the two cell populations at an early stage of Schwann cell differentiation. Because myelination requires extensive changes in cell morphology, we have investigated the composition and structure of the Schwann cell cytoskeleton at a time when these cells become committed to myelination. Here we show that Schwann cells express a cytoskeletal protein of M(r) 145 before diverging into the myelin-forming path, i.e., before they acquire cell-surface galactocerobroside. The p145 protein has the characteristics of an intermediate filament (IF) protein and immunoelectron microscopy shows that it colocalizes with vimentin, which suggests that these two proteins can coassemble into IFs. Elevated intracellular cAMP levels, which can mimic some of the early effects of axons on Schwann cell differentiation, induced p145 synthesis, therefore, we conclude that myelin-forming Schwann cells express this protein at a very early stage in their development. Immunological comparisons with other IF proteins revealed a close similarity between p145 and the neurofilament protein NF-M; the identification of p145 as NF-M was confirmed by isolating and sequencing a full-length clone from a Schwann cell cDNA library. These data demonstrate that Schwann cells remodel their IFs by expressing NF-M before acquiring the myelin-forming phenotype and that IF proteins of the neurofilament-type are not restricted to neurons in the vertebrate nervous system.

Deficient glycosylation of arylsulfatase A in pseudo arylsulfatase-A deficiency.

Deficient arylsulfatase-A activity is diagnostic of a neurodegenerative human lysosomal storage disease, metachromatic leukodystrophy. Paradoxically, similar enzyme deficiency also occurs in normal individuals, who are known as being pseudo arylsulfatase-A deficient. We showed previously that this phenotype is associated with a structural gene mutation that produces an exceptionally labile enzyme. We now report on the nature and consequence of this mutation. When the mutant arylsulfatase-A is deglycosylated by endoglycosidase H, only one smaller molecular species was generated, instead of the two from the normal enzyme. This is consistent with the loss of one of the two N-linked oligosaccharide side chains known to be present on the wild-type enzyme. Quantitative analysis of mannose and leucine incorporation showed that the mutant enzyme incorporated two- to tenfold less mannose than the normal enzyme on a molar basis. This deficient glycosylation was specific to arylsulfatase-A. Another lysosomal enzyme not affected in this mutation, beta-hexosaminidase, was glycosylated normally in the mutant cells. The remaining single oligosaccharide side chain released from the mutant arylsulfatase-A by pronase digestion was normally processed to complex and high-mannose forms. However, the high-mannose side chains contained 30% fewer phosphorylated residues than those of the normal enzyme. Nevertheless, this reduced level of phosphorylation did not prevent targeting of the mutant enzyme to the lysosomes, a process normally mediated through phosphorylated mannose residues. In conclusion, pseudo arylsulfatase-A deficiency is a unique human mutation associated with reduced glycosylation and phosphorylation of a lysosomal enzyme with the loss of one of the two carbohydrate side chains. The mutation results in greatly reduced enzyme stability, thus indicating a role for oligosaccharides in maintaining enzyme stability within the degradative environment of the lysosomes. However, the residual catalytic activity or subcellular targeting of the mutant enzyme was not affected. These properties probably account for the benign clinical presentation of pseudo arylsulfatase-A deficiency.

Heterogeneity of lysosomes in human fibroblasts.

Lysosomes are defined traditionally with the marker enzyme acid phosphatase. We showed recently that lysosomes from human fibroblasts can be separated into a light and dense fraction as well as prelysosomal population. We now provide evidence that although acid phosphatase is enriched in all three fractions, the marker enzyme in the prelysosomal compartment is qualitatively distinct from that of the lysosomes. Ultrastructural analysis showed that the acid phosphatase in the prelysosomal vesicles deposited an extremely electron-dense reaction product, entirely obliterating the lumen of the vesicle, in contrast to that of the light and dense lysosomes which deposited a fine and diffuse product scattered throughout the luminal space. Biochemical analysis showed that only 51% of the acid phosphatase in the prelysosomes was inhibited by tartrate, while 80% of that in the lysosomes was tartrate-inhibitable. Immunoprecipitation with antibodies specific for various isozymes of acid phosphatase showed that 39% of the acid phosphatase in the prelysosomes was of the 'lysosomal' type whereas over 50% of the acid phosphatase in the lysosomes was of this type. These results showed that acid phosphatase in the prelysosomes of human cultured fibroblasts can be distinguished from that of the lysosomes cytochemically, biochemically, and immunologically and that lysosomes, as marked by acid phosphatase, are a heterogeneous organelle.

Presence of a lysosomal enzyme, arylsulfatase-A, in the prelysosome-endosome compartments of human cultured fibroblasts.

Although endosomes and lysosomes are associated with different subcellular functions, we present evidence that a lysosomal enzyme, arylsulfatase-A, is present in prelysosomal vesicles which constitute part of the endosomal compartment. When human cultured fibroblasts were subfractionated with Percoll gradients, arylsulfatase-A activity was enriched in three subcellular fractions: dense lysosomes, light lysosomes, and light membranous vesicles. Pulsing the cells for 1 to 10 min with the fluid-phase endocytic marker, horseradish peroxidase, showed that endosomes enriched with the marker were distributed partly in the light lysosome fraction but mainly in the light membranous fraction. By pulsing the fibroblasts for 10 min with horseradish peroxidase conjugated to colloidal gold and then staining the light membranous and light lysosomal fractions for arylsulfatase-A activity with a specific cytochemical technique, the endocytic marker was detected under the electron microscope in the same vesicles as the lysosomal enzyme. The origin of the lysosomal enzyme in this endosomal compartment was shown not to be acquired through mannose 6-phosphate receptor-mediated endocytosis of enzymes previously secreted from the cell. Together with our recent finding that the light membranous fraction contains prelysosomes distinct from bona fide lysosomes and was highly enriched with newly synthesized arylsulfatase-A molecules, these results demonstrate that prelysosomes also constitute part of the endosomal compartment to which intracellular lysosomal enzymes are targeted.

Respiration of Mitochondria Isolated from Leaves and Protoplasts of Avena sativa.

Mitochondria isolated from mesophyll protoplasts differed from mitochondria isolated directly from leaves of Avena sativa in that protoplast mitochondria (a) had a lower overall respiratory capacity, (b) were less able to use low concentrations of exogenous NADH, (c) did not respond rapidly or strongly to added NAD, (d) appeared to accumulate more oxaloacetate, and (e) oxidized both succinate and tetramethyl-p-phenylene-diamine (an electron donor for cytochrome oxidase) more slowly than did leaf mitochondria. It is concluded that cytochrome oxidase activity was inhibited, the external NADH dehydrogenase had a reduced affinity for NADH, succinate oxidation was inhibited, NAD and oxaloacetate porters were probably inhibited, and accessibility to respiratory paths may have been reduced in protoplast mitochondria. The results also suggest that there was a reduced affinity of a succinate porter for this substrate in oat mitochondria. In addition, all oat mitochondria required salicylhydroxamic acid (SHAM) as well as cyanide to block malate and succinate oxidation. Malate oxidation that did not appear to saturate the cytochrome pathway was sensitive to SHAM in the absence of cyanide, suggesting that the oat mitochondria studied had concomitant alternative and subsaturating cytochrome oxidase pathway activity.

Effect of ammonium chloride on subcellular distribution of lysosomal enzymes in human fibroblasts.

Three subcellular fractions enriched in lysosomal enzyme activities have been isolated recently from human cultured fibroblasts with Percoll gradients: the dense lysosomes (DL), light lysosomes (LL), and light membranous vesicles (LM). They were shown to have different morphological, cytochemical, biochemical, and immunological properties. We now report on the dramatic but different effects of a primary amine, NH4Cl, on these subfractions. The lysosomes, as detected with a specific ultrastructural cytochemical stain for the lysosomal enzyme, arylsulfatase A, were swollen significantly in all these fractions, increasing their volumes by 64% (DL), 53% (LL), and 95% (LM), respectively. When arylsulfatase A enzyme activity was monitored, about half of the DL content was diverted to the LL. However, when newly synthesized arylsulfatase A enzyme protein was monitored with metabolic labeling and immunoprecipitation, about 80% of the enzyme protein was depleted from both the DL and LL. In contrast, neither the enzyme activity nor the newly synthesized enzyme protein of arylsulfatase A was greatly altered in the LM fraction by the treatment. Since primary amines caused newly synthesized lysosomal enzymes to diverge from the lysosomal route to a secretory pathway, it was deduced that (i) the LM fraction corresponded to a prelysosomal compartment whose lysosomal enzyme content was not affected by the amine and was thus proximal to the point of diversion between the secretory and lysosomal pathways; (ii) the LL and DL fractions were distal to the point of diversion since both fractions were depleted of their newly synthesized lysosomal enzyme; and (iii) the sorting of newly synthesized lysosomal enzyme may be different from that of the preexisting pool of the same enzyme since the LL fraction was depleted of its newly synthesized enzyme protein while accumulating excessive enzyme activity.

Light-Stimulated Changes in the Acidity of Suspensions of Oat Protoplasts: Dependence upon Photosynthesis.

Light induced an alkalinization and stimulated a subsequent acidification of the medium surrounding oat (Avena sativa L. cv Garry) leaf protoplasts. Blue light was less effective than would be predicted from photosynthetic action spectra. Nonetheless, 3-(3,4-dichlorophenyl)-1,1-dimethylurea prevented alkalinization and reduced acidification to the dark rate for protoplast suspensions exposed to all light regimes tested.Alkalinization increased in parallel with initial rates of O(2) evolution as the quantum flux density of white light was raised to 75 microeinsteins per square meter per second. Alkalinization was accompanied by a decrease in the CO(2) content of the medium; therefore, it was attributed to photosynthetically induced CO(2) uptake. The effect of CO(2) depletion on the acidity of the medium appeared to be mainly restricted to the first 15 minutes of exposure to light. Consequently, subsequent pH changes primarily reflected a constant net proton efflux. Acidification occurred in the dark, but rates of acidification increased in response to increased light approximately in parallel with changes in a concomitant net O(2) efflux. The results indicated that protoplasts could acidify the medium in response to nonphotosynthetic activity, but that photosynthesis mediated light stimulation of acidification.

Role of o(2) and mitochondrial respiration in a photosynthetic stimulation of oat protoplast acidification of a surrounding medium.

Some photosynthetically stimulated acidification of the medium by oat (Avena sativa L. cv Garry) leaf protoplasts required respiration. The requisite respiration (a) had a low apparent affinity for O(2), (b) was blocked by cyanide plus salicylhydroxamic acid, (c) characterized protoplasts and mitochondria isolated from protoplasts, (d) could be induced in leaf segments, and (e) appeared to result from an inhibition of mitochondrial respiration that included the cytochrome pathway.Carbon monoxide and cyanide prevented acidification of weakly photosynthesizing suspensions. Salicylhydroxamic acid had no effect on acidification, indicating a specific dependence upon cyanide-sensitive respiration. Photosynthesis stimulated acidification through stable products, and exogenously supplied O(2) stimulated acidification. The acidification response to O(2) was additive to the response to photosynthesis at subsaturating levels of light, indicating a common mode of action. Oligomycin prevented stimulation of acidification by low levels of photosynthetic activity; this stimulation appeared to be due to O(2)-induced increases in mitochondrial energy production. Oligomycin only partially inhibited stimulation of acidification by higher levels of light; this stimulation appeared to be partially dependent upon photophosphorylation. Therefore, oligomycin-sensitive acidification of the medium appeared to reflect changes in mitochondrial energy production in photosynthesizing protoplasts.

Effect of cimetidine on histamine-activated ATPase in human gastric mucosa.

The effect of histamine on Mg-ATPase was assessed in homogenates of gastric biopsies taken from the body and antrum of the stomach of patients with and without duodenal ulcer (DU). Histamine at concentrations greater than 10(-7) mol/l caused significant activation of this crude enzyme activity in the body mucosa from both groups of patients; maximum stimulation of enzyme activity was greater in the DU patients than in the non-DU group. No activation by histamine was found in ATPase of antral biopsies. Administration of cimetidine (1 g/day orally) to DU patients for 28 days abolished the histamine activation of the enzyme activity. Investigation of the activity of enzymes in normal biopsies showed that the effect of histamine was not shared by the specific H2 agonist, impromidine, or H1 agonist, 2-(2-aminoethyl)-thiazole, and that cimetidine inhibition of ATPase in vitro is probably not an histamine-receptor-specific effect.