Normal and pathological human gait analysis using miniature triaxial shoe-borne load cells

Miniature triaxial shoe-borne load cells are used to analyze the normal and a below knee amputee's gait. The gait of an amputee is studied from first step on a temporary pylon to a final "normal" gait on a permanent prosthesis. The amputee's gait is compared to that of the normal subject. The load cells are an effective method of analyzing normal and abnormal gait. For an amputee, it is possible to identify misalignments from the output of the various load cells. This method may also be useful for identifying and correcting problems in the painful below knee stump. These load cells are further used to compute the center of pressure of a normal subject and a below knee amputee. Analysis of the resulting patterns has been found to be extremely useful as a measure of the subject's functional mobility.     

In vivo metabolism of proapolipoprotein A-I in Tangier disease.

Tangier disease is a rare familial disorder characterized by extremely low levels of apolipoprotein A-I (apoA-I) and high density lipoproteins (HDL). In normal subjects, proapoA-I is secreted into plasma and converted to mature apoA-I by the cleavage of the amino-terminal six amino acids with the major isoprotein in plasma being mature apoA-I. In contrast, in Tangier disease there is a marked relative increase of proapoA-I as compared with mature apoA-I. ProapoA-I and mature apoA-I were isolated from normal and Tangier disease subjects, radio-labeled, and autologous apoA-I isoproteins injected into normal and Tangier subjects. The in vivo catabolism and conversion of proapoA-I and mature apoA-I in normal and Tangier disease subjects were quantitated. A comparison of the rate of catabolism of apoA-I isoproteins from plasma revealed a significantly faster rate of catabolism of both isoproteins of apoA-I in Tangier subjects when compared with normal subjects. The fractional conversion rate of proapoA-I to mature apoA-I was 3.9 d-1 in normal subjects and 3.6 d-1 in Tangier subjects. The results indicate that (a) apoA-I enters plasma as the pro isoprotein in both normal and Tangier subjects, (b) Tangier disease subjects have a normal fractional rate of conversion of proapoA-I to mature apoA-I, (c) proapoA-I is catabolized at the same rate as mature apoA-I in Tangier subjects, and (d) Tangier subjects catabolize both pro and mature apoA-I at a much greater rate than do normal subjects. Therefore, the relative increase in proapoA-I in Tangier disease is due to a marked decrease in mature apoA-I resulting from rapid catabolism of both pro- and mature apoA-I and not to defective conversion of proapoA-I to mature apoA-I.     

Differing erythrocyte membrane skeletal protein defects in alpha and beta thalassemia.

Thalassemic red cells show irregular morphology and maldistribution of glycoproteins and sialic acids. These changes are compatible with damage to the red cell membrane skeleton. To test this possibility, we systematically studied the interconnections of skeletal proteins in patients with a form of alpha thalassemia (HbH disease), in patients with beta thalassemia intermedia, and in normal individuals. Alpha- and beta-thalassemic spectrin functions normally in spectrin self-association, binding to normal inside-out vesicles (IOVs), and binding to actin in the presence and absence of normal protein 4.1. Binding of normal spectrin to beta: thalassemic IOVs is normal but alpha-thalassemic IOVs are defective and bind only half the normal amount of spectrin (66 +/- 5 vs. 120 +/- 16 micrograms spectrin dimer/mg IOV protein, respectively). A different defect is detected in beta thalassemia, in which protein 4.1 shows markedly reduced ability (48 +/- 7% of normal) to enhance the binding of normal spectrin to actin and a decreased ability to bind normal spectrin in a binary interaction, compared with normal protein 4.1 (24 +/- 1 and 43 +/- 1 micrograms protein 4.1/mg spectrin, respectively). As no quantitative deficiency of beta-thalassemic protein 4.1 is detected, we assume an acquired lesion is present, which affects about half of the protein 4.1 molecules. These findings indicate that specific, localized, yet different defects exist in the skeletal proteins of alpha- and beta-thalassemic red cells. The different molecular lesions imply that the mechanism of hemolysis and probably the interaction of unpaired globin chains with the membrane differs in the two diseases.     

Mimicry of Primary Bone Tumor

Injury to growing cartilage nearly always leads to changes that simulate a neoplasm. Because damage to cartilage is not immediately seen on x-rays, it is wise to obtain serial films before turning to biopsy. Since other portions of the normal skeletal system exhibit contours that mimic tumor, a detailed knowledge of normal anatomy and variations from normal that may appear during the years of growth is important.     

A deletion mutation in glucosephosphate isomerase (GPI Denton).

A new genetic variant form of glucosephosphate isomerase has been found in a family heterozygous for the mutant allele. The mutant enzyme, unlike other phenotypic variants, does not appear to be the result of a single amino acid replacement. The allozyme exhibits an isoelectric point of 5.7 and is thus much more acidic than the normal enzyme (pI = 9.3). The allozyme has been isolated from placenta and separated from the normal homodimer and heterodimer by isoelectric focusing. The enzyme exhibits normal Km and Ki values for the substrates and competitive inhibitors. The allozyme exhibits a normal pH optimum and thermal stability. However, the molecular specific activity of the variant enzyme as quantitated by radioimmunoassay is significantly lower than normal. Analytical gel filtration revealed that the molecular weight of the weight of the enzyme is significantly lower than the normal enzyme. These data thus suggest that the phenotype is unlike any previously reported and is due to a deletion mutation.     

The enzymatic mechanisms for deoxythymidine synthesis in human leukocytes: IV. Comparisons between normal and leukemic leukocytes

(1) Synthesis of deoxythymidine by either direct transfer of deoxyribosyl to thymine (pyrimidine deoxyribosyltransferase) or by a coupled deoxynucleoside phosphorylase mechanism is approximately twofold greater with normal leukocyte extracts (55 to 88% granulocytes) than with extracts prepared from leukocytes obtained from patients with chronic myelogenous leukemia. Activities in lymphocytes (normal or leukemic) are one-fifth the activity of normal granulocytes.(2) The lower activity in chronic myelogenous leukemia remains at 50% of normal even when patients are in hematologic remission with a normal per cent mature granulocytes in the peripheral blood.(3) The leukemic enzyme could not be distinguished from the normal by pH optima, thermal stability, or kinetic properties. The Km's for the deoxyribosyl acceptor and deoxyribosyl donors were identical for both enzymes. Both are subject to substrate inhibition by thymine and to inhibition by purine bases with similar Ki's. In addition, the transferase component of both the leukemic and the normal cell enzyme is activated by phosphate and arsenate. It appears, therefore, that there is no qualitative difference between the enzyme obtained from leukocytes of patients with chronic myelogenous leukemia and the enzyme obtained from normal leukocytes, suggesting that the difference in total cell activity is due to an actual decrease in amount of enzyme in chronic myelogenous leukemia or to a mixed cell population, one with a normal quantity of enzyme and the other with little or no active enzyme.(4) In both the normal cell and the leukemic cell extracts, transferase and phosphorylase activities could not be separated. The ratio of the two activities remained constant over a 140- and a 230-fold purification in normal and leukemic cell extracts, respectively. These and other observations indicate that transferase and phosphorylase activities are associated with the same protein.(5) The metabolism of pyrimidine and purine deoxynucleosides is similar for normal and leukemic cells. Catabolism of all deoxynucleosides tested was by direct phosphorolysis, except for deoxyadenosine which required initial deamination to deoxyinosine before phosphorolysis. In contrast to the greater rates of pyrimidine deoxynucleoside synthesis and cleavage with normal leukocyte extracts, the rates of purine deoxynucleoside synthesis and cleavage were approximately twofold greater with extracts prepared from cells of patients with chronic myelogenous leukemia. There was no significant difference in the rate of phosphorolytic cleavage of pyrimidine nucleosides (uridine) between the CML and normal leukocyte extracts.     

Distribution of cellular prion protein in normal human cerebral cortex--does it have relevance to Creutzfeldt-Jakob disease?

Creutzfeldt-Jakob disease and bovine spongiform encephalopathy are the best known forms of prion diseases. A basis for their pathogenesis is the transformation of normal prion protein to abnormal prion protein. This would mean that either loss of normal function or a gain of a toxic function of the prion protein would play a major role. Since the prime target for Creutzfeldt-Jakob disease in humans is the neocortex, and the intracortical distribution of the destructive process in prion diseases appears not to be haphazard, it may be that a clear cortical study of normal prion protein production in the premorbid human neocortex might contribute to insight in the pathogenesis of prion diseases. As no such study is available, we performed a detailed study in normal human cortex using immunohistochemistry for prion protein, in both frozen and vibratomised tissue, and in situ hybridisation for prion protein mRNA. We have found normal prion protein production mainly in the upper cortical neurons in neocortex and Purkinje cells in the cerebellum. This finding implicates that normal prion protein is more important as an anti-apoptotic signal in disease than abnormal prion protein is as a toxic substance.     

Unrecognized high blood pressure. A major public health issue for the workplace.

Hypertension continues to be prevalent in the general population despite the public's increased awareness of cardiovascular disease. Population-wide detection and prevention of hypertension are high priority goals within preventive health care. According to recent National Heart, Lung, and Blood Institute (NHLBI) guidelines, high normal blood pressure (BP) (systolic 130 to 139 mm Hg or diastolic 85 to 89 mm Hg) is not an innocuous condition (NHLBI, 1997). High normal BP is a detectable, modifiable, antecedent condition to overt hypertension. Little is known about the incidence of high normal BP in the general population and of its relationship to stress. This study examined the prevalence of high normal and hypertensive levels of blood pressure in a convenience sample of 94 volunteer employees from a midsize corporation. Blood pressure and level of reported stress were assessed. Findings revealed rates of 11% and 30% high normal and hypertensive blood pressure levels, respectively. Ninety-six percent of participants assumed their blood pressures were normal. As in other studies, those employees with hypertensive blood pressure reported higher stress levels than normotensive employees. However, the population with high normal BP did not report significantly higher stress levels than normotensive employees. These findings suggest high normal and hypertensive blood pressures are prevalent cardiovascular disease risk factors among employees in the workplace. Most employees are unaware of their elevated BP and the risk of high normal BP. Occupational health nurses are in a strategic position to take a proactive approach to population-wide hypertension prevention by initiating worksite BP screening and education programs.     

EXPERIMENTS ON THE R?LE OF LYMPHOID TISSUE IN THE RESISTANCE TO EXPERIMENTAL TUBERCULOSIS IN MICE

Mice either normal or splenectomized after exposure to X-ray are markedly more susceptible to bovine tuberculosis than are normal animals. Animals splenectomized a short time prior to inoculation are also more susceptible than normal, while those splenectomized eight to ten days before inoculation have about the same resistance as normal. The mice splenectomized three to four weeks before inoculation have a resistance increased over the normal, as has already been shown by Lewis and Margot. As X-ray in the doses used apparently affects only the lymphoid tissue and as the hypertrophy of the remaining lymphoid tissue after splenectomy is so rapid that the circulating lymphocytes may be much above the normal by the third week, it is concluded that this evidence, taken with the well known association of the lymphocytes with tuberculous lesions, points strongly to the lymphocyte as an important agent in the defensive mechanism against tuberculosis.     

Occurrence of an incomplete C8 molecule in homozygous C8 deficiency in man

Sera from unrelated individuals with recurrent Neisserial infections lacked C8 hemolytic activity, but contained a protein that is antigenically related to C8. Immunochemical analysis revealed complete identity of the C8-related protein of all three sera and a marked antigenic deficiency compared with normal C8. The C8-related protein was isolated from serum by adsorption to immobilized anti-C8 IgG, elution with 3 M guanidine, and subsequent gel filtration. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, the abnormal protein resembled the alpha-gamma subunit of normal C8 with respect to mobility and its ability to be cleaved upon reduction into the alpha and gamma chains. The beta chain present in normal C8 was absent. Sedimentation equilibrium analysis indicated a molecular weight of 86,000 for the abnormal C8 protein, which is identical to that of the alpha-gamma subunit of normal C8. Amino acid analysis revealed no significant difference between the abnormal C8 and normal alpha-gamma. Unlike normal C8, the abnormal protein did not bind to EAC1-7 or to SC5b-7; however, upon addition to the deficient serum of beta chain isolated from normal C8, hemolytic activity was restored and formation of SC5b-9 occurred. We concluded that the dysfunctional C8 protein in the three individuals' serum is identical to the alpha-gamma subunit of normal C8 and that this form of C8 deficiency is distinct from the C8 deficiencies previously reported in which the entire three-chain protein is lacking.     

Oxygen transport in a woman with hemoglobin Hope/beta+ thalassemia.

Because their blood may "unload" oxygen more readily than normal, people with hemoglobin of low oxygen affinity might be expected to be anemic. We have studied a woman with hemoglobin Hope/beta+ thalassemia, whose hemoglobin level was 10.4 to 12.3 gm/dl (normal 14 +/- 2) despite a P50 of 41 mm Hg (normal 26). Her cardiac index was normal, yielding a calculated mixed venous PO2 of 51 mm Hg (normal 34 to 49). Oxygen transport in patients with low oxygen affinity can be maintained by a variety of homeostatic responses, only one of which is altered erythropoiesis.     

In vivo metabolism of a mutant form of apolipoprotein A-I, apo A-IMilano, associated with familial hypoalphalipoproteinemia.

Apo A-IMilano is a mutant form of apo A-I in which cysteine is substituted for arginine at amino acid 173. Subjects with apo A-IMilano are characterized by having low levels of plasma HDL cholesterol and apo A-I. To determine the kinetic etiology of the decreased plasma levels of the apo A-I in these individuals, normal and mutant apo A-I were isolated, radiolabeled with either 125I or 131I, and both types of apo A-I were simultaneously injected into two normal control subjects and two subjects heterozygous for apo A-IMilano. In the normal subjects, apo A-IMilano was catabolized more rapidly than the normal apo A-I (mean residence times of 5.11 d for normal apo A-I vs. 3.91 d for apo A-IMilano), clearly establishing that apo A-IMilano is kinetically abnormal and that it has a shortened residence time in plasma. In the two apo A-IMilano subjects, both types of apo A-I were catabolized more rapidly than normal (residence times ranging from 2.63 to 3.70 d) with normal total apo A-I production rates (mean of 10.3 vs. 10.4 mg/kg per d in the normal subjects). Therefore, in the subjects with apo A-IMilano, the decreased apo A-I levels are caused by rapid catabolism of apo A-I and not to a decreased production rate, and the abnormal apo A-IMilano leads to the rapid catabolism of both the normal and mutant forms of apo A-I in the affected subjects.     

Sonography of extraaxial fluid in neurologically normal infants with head circumference greater than or equal to the 95th percentile for age.

The goal of this study was to examine sonographically the extraaxial space in neurologically normal infants with occipital frontal circumference greater than or equal to the 95th percentile for age and correlate these dimensions with neurologic follow-up findings to determine a range of normal values. We thus hope to obviate unnecessary workup of these patients, including additional imaging or intervention. Our results demonstrate that for infants with a craniocortical width or sinocortical width less than 10 mm, the negative predictive value and specificity for developing a neurologic abnormality during the 55 week follow-up period were 94 to 100%. Thus, for neurologically normal infants with occipital frontal circumference greater than or equal to the 95th percentile for age and a head ultrasonogram that is otherwise normal, a craniocortical or sinocortical width of up to 10 mm can be considered within normal limits. Clinical follow-up evaluation is prudent, but additional imaging of these infants is not required.     

Abnormal Plasminogen: A HEREDITARY MOLECULAR ABNORMALITY FOUND IN A PATIENT WITH RECURRENT THROMBOSIS

A patient who suffered a recurring thrombosis over the last 15 yr has been investigated. The only abnormality found in this patient was a significantly depressed level of plasminogen activity in plasma. In spite of the depressed plasminogen activity, the patient was found to have a normal level of plasminogen antigen concentration. It was calculated that the activity per milligram of plasminogen of the patient was approximately one-half the values of normal subjects. The same discrepancy between biological activity and antigen concentration was found in the other members of the kindred. A niece was found to have practically no plasminogen activity but possessed a normal concentration of plasminogen antigen. Both her parents were found to have approximately half the normal plasminogen activity and normal antigen levels. These studies suggested that the molecular abnormality was inherited as an autosomal characteristic, and the family members who had half the normal levels of activity with normal plasminogen antigen were heterozygotes whereas the one with practically no plasminogen activity was homozygote. Subsequent studies showed that the pattern of gel electrofocusing of purified plasminogen of the heterozygotes consisted of 10 normal bands and 10 additional abnormal bands, each of which had a slightly higher isoelectric point than each corresponding normal component. This indicates that plasminogen of the heterozygote is a mixture of normal and abnormal molecules in an approximately equal amount, which was substantiated by active site titration of purified plasminogen preparations obtained from the propositus and a normal individual. The gel electrofocusing pattern of the homozygote consisted of abnormal bands only. The defect is a hereditary abnormality of plasminogen.     

Physical activity in the young

Appropriately chosen and supervised physical activity promotes normal growth and is beneficial in treating some diseases; it can also help a child adjust to a physical handicap. Participation in general or team sports is not only enjoyable but also important to normal physical, mental and emotional development. A child's activity level can indicate both normal variations in growth and possible medical problems.     

Indentation stiffness does not discriminate between normal and degraded articular cartilage

BACKGROUND: Relative indentation characteristics are commonly used for distinguishing between normal healthy and degraded cartilage. The application of this parameter in surgical decision making and an appreciation of articular cartilage biomechanics has prompted us to hypothesise that it is difficult to define a reference stiffness to characterise normal articular cartilage. METHODS: This hypothesis is tested for validity by carrying out biomechanical indentation of articular cartilage samples that are characterised as visually normal and degraded relative to proteoglycan depletion and collagen disruption. Compressive loading was applied at known strain rates to visually normal, artificially degraded and naturally osteoarthritic articular cartilage and observing the trends of their stress-strain and stiffness characteristics. FINDINGS: While our results demonstrated a 25% depreciation in the stiffness of individual samples after proteoglycan depletion, they also showed that when compared to the stiffness of normal samples only 17% lie outside the range of the stress-strain behaviour of normal samples. INTERPRETATION: We conclude that the extent of the variability in the properties of normal samples, and the degree of overlap (81%) of the biomechanical properties of normal and degraded matrices demonstrate that indentation data cannot form an accurate basis for distinguishing normal from abnormal articular cartilage samples with consequences for the application of this mechanical process in the clinical environment.     

经阴道彩超检测黄体血流对胚囊发育的研究

本文研究目的是经阴道彩超检测早期妊娠黄体血流阻力指数，做为预测胚囊正常发育的参数值。研究内容采用实验组与对照组在早孕期间（孕３６～６５天），经阴道彩超常规检测妊娠黄体血流阻力指数后，对早妊胚囊分别进行临床病理检验和影像跟踪观察，最后筛选出病检具有正常绒毛组织和超声检测发育至１８周为正常胎儿的早妊黄体血流阻力指数值，做统计学处理。研究结果表明：本文中所测得的黄体血流阻力指数（两组共计６０例），均能维持胚芽的正常发育。两组均值无显著性差异，均服从于正态分布ｔ＝０．０２６３７＜０．０５，Ｐ＞０．０５两组正态分布的总体均值是相同的。从而说明一定范围内的黄体血流阻力指数可作为判别早妊胚囊发育正常的参考值     

Plasma membrane potential of lymphocytes from ataxia telangiectasia patients

The plasma membrane potential of lymphocytes prepared from ataxia telangiectasia (AT) patients and normal subjects was assessed using the optical indicator bis-(3-phenyl-5-oxoisoxazol-4-yl) pentamethineoxonol (oxonol-V). AT lymphocytes had a potential of -46 +/- 9 mV and normal lymphocytes had a potential of -63 +/- 4 mV. The intracellular cation content (Na+ and K+) of AT and normal lymphocytes was similar. AT and normal lymphocytes were both depolarized by extracellular K+ and to a similar extent. This study indicates that one feature characterizing ataxia telangiectasia is a modification of the ability of the lymphocyte cell membrane to sustain a normal membrane potential.     

The uri nary excretion of 2-phenylethylamine in phenylketonuria

The urinary concentrations of free and conjugated 2-phenylethylamine were determined in phenylketonuric patients and normal subjects by solvent extraction and gas chromatography. Free 2-phenylethylamine excretion was found to be significantly elevated above normal in phenylketonuric adults and children receiving a normal or a slightly restricted intake of phenylalanine. Urinary 2-phenylethylamine was also significantly increased in phenylketonuric children receiving low phenylalaine dietary therapy. Conjugated 2-phenylethylamine excretion was found not to be increased above normal. In the light of these results, a relationship between blood phenylalanine concentration and 2-phenylethylamine excretion is proposed, and the possible role of this amine in phenylketonuria is discussed.     

Keeping normal labor normal

Labor and delivery have been viewed by physicians as processes that can and must be managed by physicians for their pregnant patients. This article asserts that most births do not need to be interventionally managed and that a birth attendant's highest order skill is knowing when and how not to intervene. Further, the article looks at what birth interventions are likely to keep normal labor normal. The authors propose a new paradigm: The 10 "P's" of keeping normal labor normal.