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Biomedical subjects

R G Miller

Publications and source records attributed to R G Miller.

At least 181 records · Page 10Linked to original sources
PubMed1991

Depression of thymus-dependent immunity in wasting protein-energy malnutrition does not depend on an altered ratio of helper (CD4+) to suppressor (CD8+) T cells or on a disproportionately large atrophy of the T-cell relative to the B-cell pool.

We report cell numbers within major subsets of lymphocytes in the spleen, mesenteric nodes, and recirculating pool of weanling mice subjected to protein-energy malnutrition (PEM). PEM and thymus (T)-dependent immunodepression were induced in male C57BL/6J mice by a low-protein (LP) diet fed ad libitum. Recirculating lymphocyte numbers were estimated by enumerating labeled and unlabeled cells after equilibration of a known number of fluorescein isothiocyanate-labeled C57BL/6J donor lymphocytes within well-nourished or LP recipients. Involution of the recirculating lymphocyte pool of the LP group was proportionately less than the lymphoid atrophy of the spleen and mesenteric nodes. The LP protocol exerted no influence on the ratio of helper (CD4+) to suppressor (CD8+) T cells and increased the ratio of T cells to B cells in the secondary lymphoid organs and recirculating pool. These results challenge two established concepts: that T-dependent immunodepression in PEM depends on a reduced CD4(+)-CD8+ ratio and that PEM induces greater involution within the T-cell system than within the B-cell system.

Animals↗
PubMed1991

Neurophysiology of postviral fatigue syndrome.

The exact pathophysiology of excessive fatigue in patients with postviral fatigue syndrome (PVFS) remains uncertain in spite of increasing investigation. One objective abnormality of neuromuscular function is the increased jitter on single fibre EMG studies. While this is a sensitive technique which indicates a disturbance in the peripheral part of the motor unit, it is non-specific and its role in the pathophysiology remains unclear. Impaired muscular activation with added force in response to superimposed electrical stimulation suggests an extra-muscular and/or central component of fatigue. Conventional neurophysiological studies and those of strength and endurance have shown no objective abnormality in patients compared with controls. The previous reports of disturbed muscle metabolism on NMR spectroscopy have not been confirmed in more recent studies and no consistent abnormality of excitation-contraction coupling has so far emerged. Finally, unlike patients with depression, cognitive evoked potential studies suggest impaired attention, memory and stimulus evaluation in postviral fatigue syndrome. In future studies, the importance of utilising approved clinical criteria for patient inclusion cannot be overemphasized. Control groups should include sedentary or deconditioned as well as depressed subjects to help standardise these important variables.

Electromyography↗
PubMed1991

The effect of spine fusion on respiratory function in Duchenne muscular dystrophy.

Serial measures of respiratory function were made in 17 patients with Duchenne muscular dystrophy who underwent segmental spine fusion and in 22 patients who did not. No significant differences were observed between the 2 groups (operated vs. nonoperated) in terms of declining respiratory function. Nonetheless, all operated patients reported either improved sitting comfort, appearance, or both. Thus, our results suggest that there are distinct benefits from segmental spine fusion; however, there was no salutary effect upon respiratory function either in the short term or after up to 5 years follow-up.

Adolescent↗
PubMed1991

Subacute, reversible motor neuron disease.

Four patients with a clinical syndrome closely resembling amyotrophic lateral sclerosis recovered completely, without treatment, 5 to 12 months after onset. Electrodiagnostic tests revealed acute and chronic denervation, with normal motor and sensory nerve conduction studies. The CSF was normal, and tests for paraproteinemia, heavy metal intoxication, and systemic illness were negative. Although such cases are rare, the possibility of spontaneous recovery should always be considered when counseling patients with suspected ALS.

Adult↗
PubMed1991

Fatigue and myalgia in AIDS patients.

Fatigue and myalgia are common in patients with acquired immunodeficiency syndrome (AIDS). To determine whether altered muscle metabolism or impaired activation of muscle might account for these symptoms, we utilized three different exercise protocols to produce fatigue in nine AIDS patients who complained of both fatigue and exercise-exacerbated myalgia. Five were taking azidothymidine (AZT), which may cause a mitochondrial myopathy. Simultaneous measures of force, EMG, and muscle metabolites (phosphocreatine, inorganic phosphate, adenosine triphosphate, and intracellular pH) using phosphorus nuclear magnetic resonance spectroscopy were performed during fatigue and recovery. There were no significant differences between patients and controls in terms of fatigability, muscle metabolism, or muscle activation. These results provide no support for the hypothesis that fatigue or myalgia in AIDS patients derives from altered muscle metabolism or that AZT produces mitochondrial myopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Repeat thymectomy in chronic refractory myasthenia gravis.

Encouraged by recent results with "extended" thymectomy in the treatment of myasthenia gravis, we carried out repeat thymectomy in six patients with chronic, refractory disease who did not initially have extended thymectomy. All were completely disabled with longstanding myasthenia. Initial thymectomy (four transsternal, one transcervical, and one substernal) was carried out at a mean of 8.9 years previously (range, 5 to 18). There was no residual thymus observed with CT, but at repeat thymectomy, residual thymic tissue was present in five of six patients. Five patients significantly improved and four returned to full-time work. Mean prednisone dose declined from 51 mg to 18 mg/d, and mean pyridostigmine dose fell from 1,290 mg to 415 mg/d. No patient to date has had a complete remission. These results suggest that repeat thymectomy may benefit some patients with chronic disabling myasthenia gravis, especially when it is uncertain from a review of the operative report whether all thymic tissue was removed at the initial thymectomy.

Adult↗
PubMed1991

Prognosis in AZT myopathy.

The myopathy caused by zidovudine (AZT) appears to be common but is incompletely characterized, particularly regarding prognosis. Twenty patients with HIV infection developed a necrotizing myopathy while taking AZT for 9 to 30 months. Ten presented with myalgia and 17 with proximal muscle weakness. Serum CK was elevated in all (two to 11 times normal), and EMG suggested active myopathy in all but two. There were scattered granular degenerating fibers, with scant or no inflammation, in a pattern consistent with a toxic myopathy in all 18 patients biopsied. Three patients with an HIV-related inflammatory myopathy were distinguished by histologic differences. After stopping AZT (n = 15), myalgia promptly resolved (10 of 10). Strength improved more slowly with 12 of 15 regaining normal or nearly normal strength, but three have persistent weakness. CK returned to normal in 12 of 15, and follow-up EMG (n = 11) documented reduced fibrillation density in all 11 patients. These findings underscore the need for early diagnosis of this reversible myopathy.

Adult↗
PubMed1991

Autosomal recessive distal dystrophy.

We describe five new cases of autosomal recessive distal dystrophy (Miyoshi myopathy) and emphasize the distinctive clinical and laboratory features of this unusual muscular dystrophy. Symptoms began at age 15 to 25, the gastrocnemius muscles were selectively involved, and creatine kinase was elevated more than 10 times normal. The EMG showed abundant brief motor units with numerous fibrillations. Dystrophic features without vacuoles were best seen in the biceps femoris muscle. Asymptomatic creatine kinase elevation was present years prior to the development of weakness. The disorder appears to be inherited in an autosomal recessive pattern. Miyoshi myopathy can be distinguished from other distal muscular dystrophies. We propose a new classification for the distal muscular dystrophies.

Adolescent↗
PubMed1991

Xylose-lysine-tergitol 4: an improved selective agar medium for the isolation of Salmonella.

A study was conducted to evaluate a new selective plating medium for isolating Salmonella using pure bacterial cultures, and poultry environmental specimens containing high numbers of competing enteric bacteria. Xylose-lysine-tergitol 4 (XLT4) agar was found to strongly inhibit Proteus, Pseudomonas, Providencia, and many other nonsalmonellae and to provide good differentiation between Salmonella and Citrobacter. The XLT4 medium significantly improved Salmonella isolation from chicken farm environmental drag-swab samples over the other selective plating media evaluated.

Animals↗
PubMed1990

Generation and characterization of peptide-specific, MHC-restricted cytotoxic T lymphocyte (CTL) and helper T cell lines from unprimed T cells under microculture conditions.

We describe a microculture system for the generation of CTL and T helper cells against peptides. Tryptic digest and cyanogen bromide fragments of chicken ovalbumin and synthetic peptides of ovalbumin (323-339) and influenza virus (NP 365-380) were used to generate CTL and T helper lines from unprimed T cells. These lines were both peptide-specific and MHC-restricted. The relative ease of generating peptide-specific, MHC-restricted CTL and helper T cell lines with as few as 10(6) unprimed lymphocytes can be an efficient method of detecting potential immunogenic determinants of an antigen.

Animals↗
PubMed1990

Development of T cells in vitro from precursors in mouse bone marrow.

Bone marrow cells from 6- to 8-week-old athymic nude mice were depleted of nylon-wool adherent cells and cultured in vitro at low cell numbers (300 cells/well) in medium supplemented with a supernatant from a thymoma cell line. About 1% of cultured cells grew. Pooled cultures contained cells expressing CD3 (52%), CD4 (37%), CD8 (11%), Thy 1.2 (72%), MAC-1 (43%) and J11d (86%) but no cells expressing sIg. They also contained cells expressing mRNA for the alpha, beta, gamma, and delta chains of the T cell receptor as assessed with C region probes using a sensitive dot blot assay. These cells appear to develop from progenitors which are CD3-. When pooled Day 10 cultures were depleted of nylon-wool adherent cells, the remaining cells were nearly all J11d+, Thy 1.2+, MAC-1-, CD3+, and either CD4+CD8+; CD4+CD8-; CD4-CD8+, or CD4-CD8-; i.e., their surface marker patterns were reminiscent of those of thymocytes. We conclude that our culture system is enabling bone marrow precursors to commence differentiation down the T cell lineage in the absence of a thymic environment.

Animals↗
PubMed1990

Characterization of cells with T cell markers in athymic nude bone marrow and of their in vitro-derived clonal progeny. Comparison with euthymic bone marrow.

Evidence is presented that early steps in T cell differentiation, to the point of TCR expression, can occur in athymic nude bone marrow (BM) and perhaps also in normal BM. Low density nylon wool nonadherent BM from 5- to 8-wk-old nude and normal mice was found to contain dim CD3+ CD4- CD8- cells. This subpopulation was not found in scid/scid low density nylon wool nonadherent BM but was present at similar frequency in both nude and normal BM and expressed comparable fluorescence intensity. With the use of additional markers, a difference between nude and normal dim CD3+ CD4- CD8- cells was found: the ratio of J11d+/J11d- cells was at least threefold higher in nude than in normal BM. Whereas 60% of nude J11d+ CD3+ cells expressed a TCR-alpha/beta and 40% expressed a gamma/delta TCR, almost no TCR-gamma/delta expressing cells were detected in dim CD3+ cells from normal mice in either the J11d+ or J11d- subpopulation. The majority of those cells express a TCR-alpha/beta. We established that nude dim CD3+ CD4- CD8- cells were distinguishable from mature recirculating T cells and developed an in vitro clonal culture system that supported the growth of these cells. When these cells were cocultured in vitro in a limiting dilution system with inactivated anti-CD3 mAb-secreting cells, in the presence of rIL-2 and rIL-4, one in 5 x 10(2) to 1 x 10(3) cells were growth inducible. Most progeny cells expressed a CD3+ CD8+ CD4- surface phenotype. Cultures displayed nonspecific cytolytic reactivity. With the use of a sensitive dot-blot technique, transcripts coding for C alpha, C beta, VC gamma, and C delta TCR genes were detected in these cultures. Rehybridization experiments demonstrated mutually exclusive expression of either C alpha or C delta mRNA transcripts in the majority of clones selected for a high probability of clonality. Most (greater than 95%) of T cell clones derived from normal BM expressed the C alpha transcript with approximately 5% expressing the C delta transcript. In contrast, about 40% of T cell clones derived from nude BM expressed the C delta transcript whereas the remaining 60% expressed 10-fold lower C alpha message than normal BM-derived clones.

Animals↗
PubMed1990

The electrophysiologic profile of Dejerine-Sottas disease (HMSN III).

Electrophysiologic studies in 11 patients with Dejerine-Sottas disease (hereditary motor and sensory neuropathy type III, HMSN III) showed median and ulnar motor nerve conduction velocities less than 6 m/sec in all but 1 patient. Marked temporal dispersion without conduction block was present in all patients. Uniform slowing in adjacent motor nerves was consistent with other studies of inherited neuropathies, although marked temporal dispersion may make HMSN III more difficult to distinguish from acquired neuropathies than other hereditary conditions. The electrophysiologic features of HMSN III patients were significantly different from a series of patients with other hereditary neuropathies chosen because of very slow nerve conduction velocity.

Adolescent↗
PubMed1990

Direct effect of cyclosporin A on CD8+ T lymphocytes in a primary mixed lymphocyte reaction.

Cyclosporin A (CsA) blocks the development of cytotoxic T lymphocytes (CTL) in a primary mixed lymphocyte reaction (MLR) when added during the first few days of culture. We found that addition of recombinant IL-2 (rIL-2) or an IL-2-containing supernatant (2 degrees MLR SN) either alone or in combination was unable to reverse the suppression. Purified CD8+ responder cells were inhibited as effectively by CsA as unfractionated cells, suggesting that CsA has a direct, lymphokine-independent effect on CD8+ cells. The frequency of CTL precursors (CTLp) responding in a primary MLR was measured by limiting dilution in the presence and absence of CsA. Using either unfractionated cells or cell-sorter-purified CD8+ responder cells, no suppression was seen at very low cell numbers but increased markedly as the cell number per culture increased. These results imply that either a CD8+ regulatory/suppressor cell is being diluted out at low cell numbers, or that low cell-density culture conditions might override the inhibitory effects of CsA.

Animals↗
PubMed1990

Effect of cyclosporine on secondary cytotoxic T lymphocyte responses.

Cyclosporine, a potent immunosuppressive agent, inhibits the development of the cytotoxic response in a secondary mixed lymphocyte reaction (MLR) in a dose-dependent manner. Exogenous lymphokines can partially overcome this inhibition. We present evidence that the CsA-resistant cells detected in these responses represent an activated population of memory CTL precursors that require only lymphokines for clonal growth and that kill targets of the original stimulator type only. Recombinant IL-4, when used at high concentrations, can support the generation of CTL in the presence of CsA during a secondary MLR response. The magnitude of the cytotoxic response though is far below the maximal levels achieved either by saturating quantities of rIL-2 or a combination of subsaturable quantities of rIL-2 and rIL-4.

Animals↗
PubMed1990

Constant relationships between force, phosphate concentration, and pH in muscles with differential fatigability.

We examined the relationships between muscle force and both phosphate and hydrogen ion concentrations in muscles with differential fatigability and in different types of exercise. We measured force and 31phosphorus nuclear magnetic resonance spectra from the tibialis anterior (a slow-contracting, fatigue resistant, postural leg muscle) during a sustained maximum contraction (anaerobic exercise) and during intermittent contractions (aerobic exercise). We observed similar relationships between the decline in muscle force during fatigue and changes in both phosphate and hydrogen ion concentrations during both aerobic and anaerobic exercise in tibialis anterior. Furthermore, these relationships were similar to those previously observed in the adductor pollicis. The demonstration of constant relationships between muscle contraction force and metabolism under different exercise conditions and in muscles of different function supports the view that both phosphate and hydrogen ions are important regulatory factors in the fatigue of human muscle.

Adenosine Triphosphate↗