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Biomedical subjects

W J Williams

Publications and source records attributed to W J Williams.

At least 91 records · Page 5Linked to original sources

Quantitation of motion perception in the digits: a psychophysical study in normal human subjects.

Threshold perception of motion of the digits was obtained in 14 normal subjects. The metacarpophalangeal joint of the index and the fifth finger of each hand and the metatarsophalangeal joint of the hallux of each foot were passively moved up and down with respect to a horizontal plane defined by the palmar or plantar surface. The motion was sinusoidal at frequencies of 0.5 and 5.0 Hz. A mpdified von Békésy paradigm similar to that used in audiometry was utilized to yield threshold levels of motion sensation. There was little difference in the thresholds obtained for the different joints. The difference between high- and low-frequency stimulation, however, was significant (p less than 0.001): the 0.5 Hz threshold was found to range from 0.8 to 1.0 degree, whereas the 5.0 Hz threshold varied from 0.4 to 0.6 degree. It is thought that motion sense is largely dependent on joint receptor contributions, but muscle and cutaneous receptors may also contribute to this proprioceptive sensation.

Adolescent↗

Sarcoidosis--1977.

Sarcoidosis is defined as a multisystem disorder characterised by the finding of epithelioid cell granulomas in more than one system. Diagnosis is aided by the use of the Kveim Siltzbach skin test and the development of an "in vitro" Kmif test is discussed. Despite extensive researches the causative agent(s) remains unknown. The granulomas, morphologically, on light and electron microscopy and histochemistry may be indistinguishable from those caused by known agents. Inclusion bodies are also non specific. Central necrosis is rare, and can be usually distinguished from caseation. The close relationship between the monocyte derived, epithelioid cells and lymphocytes is emphasised. Evidence is accumulating that epithelioid cells in sarcoid type granulomas are primarily synthesising rather than phagocytic cells. The products are considered to be mucoglycoproteins and may have both local and systemic actions. Locally it is suggested that the products may be lymphokines which react with associated thymic derived (T) lymphocytes and mononuclear cells and thus play a role in perpetuating the granulomas. Epithelioid cells may also be a source of circulating T lymphocyte function depressants. It has further been suggested that epitheloid cells are the source of the raised angiotensin converting enzyme found in sarcoid sera. Study of epithelioid cell granulomas in sarcoidosis, despite the disappointing lack of evidence of a causative sarcoid agent(s), is thus of considerable interest in furthering knowledge of many diseases characterised by these curious cellular foci.

Granuloma↗

Neurological manifestations of aging.

A group of 51 socially active, self-declared neurologically normal subjects ranging from 61 to 84 years of age were studied with a battery of clinical neurological examinations and a semiquantitative vibration perception test. None of the subjects showed a consistent pattern of neurological deficit that could be identified as pathological. On review of systems, the most frequent complaints were difficulty remembering names, numbness and tingling of fingers and toes, and headaches. In the neurological examination, the most commonly observed abnormalities were positive palmomental reflex, snout reflex, abnormalities in pursuit eye movements, convergence insufficiency, and minor mistakes in perception of light touch. There was no apparent trend of worsening of symptoms and signs with advancing age. In the semiquantitative testing of vibration perception, there was a slight trend toward worsening of vibration perception in the upper and lower extremities with advancing age. Motor abnormalities were absent, and there were relatively few subjects who showed reflex abnormalities. This study confirms the previously reported diminution of vibration perception with aging. Caution must be exercised before attributing myotatic reflex and motor abnormalities to the aging process alone.

Aged↗

Role of in vitro and in vivo tests of hypersensitivity in beryllium workers.

The value of the beryllium macrophage migration inhibition (Be MIF) and Mantoux tests in the diagnosis of chronic beryllium disease and in the detection of hypersensitivity in healthy beryllium workers is demonstrated. In the absence of steroid treatment the Be MIF test is positive in chronic beryllium disease patients. Seven of 50 (14%) helathy beryllium workers were Be MIF positive, while all the control subjects, normal and sarcoidosis patients, were negative. Healthy beryllium workers tend to be more often Mantoux negative than a comparable group of non-exposed workers, and although not conclusive this finding correlates with a positive Be MIF test. Although the detection of hypersensitivity is not diagnostic of disease, the Be MIF test can be used as an additional method for monitoring the health of beryllium workers. The full significance of our results should be assessed by a long-term study.

Adult↗

Halothane macrophage migration inhibtiion factor test in halothane-associated hepatitis.

As an index of delayed hypersensitivity in vitro halothane macrophage migration inhibition factor tests (halothane-MIF tests) were performed on peripheral blood lymphocytes from five patients with halothane hepatitis. Twenty-two subjects exposed to halothane, but with no evidence of jaundice, five 'healthy' hospital anaesthetists, nine jaundiced subjects without halothane exposure, and 10 healthy subjects with no history of exposure to halothane were also tested. The halothane-MIF test was positive in four of the five patients with halothane-induced hepatitis; the negative result was in a patient on steroid treatment. The test was negative in all other subjects. Our findings suggest that the halothane-MIF test may be of value in the diagnosis of halothane-induced hepatitis and as a screeening procedure for the identification of susceptible subjects.

Adult↗

A search for thymie (T) lymphocyte inhibitory factors in sarcoid sera.

Sarcoid patients frequently show depression of skin delayed hypersensitivity reactions suggesting depression of thymic (T) lymphocyte function. In vitro demonstration of such depression, however, to date, is inconclusive. We have used the macrophage migration inhibition test with Kveim "antigen" (KMIF), and spontaneous sheep red cell rosetting (SRC) techniques as indicator systems. We found that a positive KMIF test obtained in 7 of 16 subjects (13 sarcoid and 3 non sarcoid) in the presence of foetal bovine sera (FBS) became negative in the presence of sarcoid patients sera. Using lymphocytes from a single normal healthy subject the SRC tests were performed in the presence of sarcoid, normal healthy sera and FBS. With sarcoid sera 38% of lymphocytes showed rosetting as compared with normal human sera, 54%, and with FBS, 57%. Where lymphocytes were pre-incubated for one hour in the various sera the percentage of rosetting cells were even further reduced, sarcoid sera 23%, as compared to normal human sera, (49%), and FBS, (54%). Thus, using two tests of lymphocyte function our preliminary results suggest the presence of T cell inhibitory factors in sarcoid sera.

Adult↗

Form and function of sarcoid granulomas.

The pathological feature of sarcoidosis is the presence of granulomas in more than one system. What is a granuloma? Morphologically a granuloma consists of a focal collection of mononuclear, epithelioid cells, sometimes giant cells, odmixed and surrounding lymphocytes, plasma cells and fibro-blasts. Inclusion bodies, Schaumann and asteroid, may be present. Necrosis may be present or absent. All are features of chronic inflammation, and unfortunately are not diagnositc of any one causative agent. The cell characteristic of granulomatous inflammation is the bone marrow derived epithelioid cell. Epithelioid cells are metabolically active and in some diseases, such is tuberculosis, behave as phagocytic macrophages. What is the function of epithelioid cells in sarcoidosis? It is potentially phagocytic but has never been shown to contain any indentifiable infective agents. It has all the potentials of a synthesising cell whose products may well influence persistence of the granulomas. A detailed study of the nature and function of epithelioid cells in sarcoidosis will be presented based on light and electron microscopy, histochemistry and tests of lymphocyte function.

Cell Nucleus↗

The fine structure of dense lysosomes isolated from rat spleen.

A dense fraction from rat spleen was shown to consist of membrane bound organelles of varying shape and size which were packed with electron dense particles with the appearance of ferritin. Electron microscope microanalysis confirmed that iron was present in the organelles and the amount correlated with the density as noted in transmission electron microscopy. The organelles also stained, positively for acid phosphatase and, therefore, confirmed the biochemical findings that dense lysosomes (L30) had been isolated. The role lysosomes play in the degradation of red blood cells, and as possible sites of iron storage, are briefly discussed.

Animals↗

The first seven cases of chronic beryllium disease in ceramic factory workers in Japan.

In the present paper the first 7 cases in Japan of chronic beryllium disease found in workers employed in a ceramic factory utilizing beryllium have been described. Immunological examinations of these cases showed changes similar to those observed in sarcoidosis, that is, negative tuberculin test and increase in serum gamma globulin and immunoglobulins. The fact that a considerable number of workers in the same factories as the patients showed negative tuberculin reaction may suggest that there may be further cases of chronic beryllium disease among them that are still in a latent period.

Adult↗

International Kveim histology trial.

An histological analysis of Kveim-test biopsies performed on a total of 306 patients including those with sarcoidosis, Crohn's disease, tuberculosis, and collagen disease is presented. Five main Kveim suspensions, "antigens," were used in the survey, Colindale K 12, Lot 5, Marburg 2 and 3, Commonwealth Serum Laboratory (CSL) early batches, 001/2/3 and late batches, 005/6. The biopsies were read blind by two observers (overall agreement 75%), the nature of the antigen and disease later disclosed, and the finding statistically analysed. It was agreed that focal epithelioid-cell collections remain as the essential criteria for the diagnosis of Kveim positivity. Diffuse epithelioid cells, Langhans' giant cells, lymphocytes, and necrosis are associated with focal epithelioid cells and hence Kveim positivity. Steroids were found to inhibit Kveim positivity. Observer disagreements were mainly due to difficulties in distinguishing macrophages from true epithelioid cells. We conclude that doubtful cells should be ignored in deciding Kveim positivity. Lymph-node-derived Kveim antigens were the most sarcoid-specific. They were more granulogenic and produced more necrosis, despite also producing the most foreign material. It is recommended that validation of new Kveim antigens must include adequate testing on patients with Crohn's disease, as the more nonspecific antigens were shown to give equal positive rates in sarcoidosis and Crohn's disease.

Adult↗

Dynamic response and transfer characteristics of joint neurons in somatosensory thalamus of the cat.

1. The dynamic response of neurons sensitive to knee joint rotation in the cat somatosensory thalamus was studied during sinusoidal variation of joint angle. The input sine waves were applied with a precise voltage-controlled, electromechanical actuator. The average rate of discharge of a single cell was considered as the output parameter. Describing functions of the sensory system were extracted by correlation and spectral analysis techniques. The effects of anesthetic, bias angle, and excursion angle were investigated. Discrete and swept sinusoidal waveforms between 0.1 and 7.0 Hz were used as inputs.2. The majority of joint cells in the thalamus were rapidly adapting and had frequency-response curves that were characterized as highpass filters. Although the major features of the response curves for individual cells were very similar, they could not all be fit with a single transfer function. The describing function of all the rapidly adapting cells averaged together was well fit by a transfer function that could be termed velocity sensitive in the bandwidth between 0.1 and 6.5 Hz. Most of these phasic cells showed a phase-locking tendency, particularly at high frequencies.3. The dynamics of the response for the rapidly adapting cells was relatively independent of anesthetic, bias angle, and excursion angle. Threshold and saturation effects were exhibited by some cells for very small (less than 1 degree) and large (greater than 10 degrees) input amplitudes, respectively. In addition a few (17%) showed a bidirectional response, i.e., responded at both flexion and extension of the limb. The anesthetic had a strong effect in depressing the spontaneous discharge of the cells and seemed to change the character of the tonic response by introducing a bursting component.4. The transfer characteristic of the thalamic cells was found to be a single-pole low-pass filter plus a time delay. The optimized value for the filter was found to have a corner frequency of 6.0 Hz with a time delay of 6 ms.5. Of the knee joint sensitive cells, 17% were slowly adapting or tonic, and more tonic cells were found in the unanesthetized animals. Only one tonic cell was studied in detail, and its dynamic characteristics were similar to that of the slowly adapting joint receptors at low frequencies. In this respect the rapidly adapting and slowly adapting joint cells in the thalamus have strikingly different frequency-response curves, the former curves have a much steeper slope in the magnitude.6. The functional implications of these results and of other recent findings in relation to the probable role of joint receptors in mediating proprioception are discussed.

Animals↗