Biomedical subjects
R G Miller
Publications and source records attributed to R G Miller.
Specific spontaneous cytotoxic activity in human T cell colonies.
Cells in T cell colonies grown in vitro from normal human peripheral blood leukocytes can kill a variety of different target cells against which the blood donor has not knowingly been previously sensitized, i.e., the colony cells exhibit spontaneous cytotoxicity. Tumor target cells are preferentially killed. The ability to kill two different targets segregates independently in different colonies, which implies that the effector cells are specificity restricted. A majority (perhaps all) of the effector cells possess receptors for sheep erythrocytes and do not possess receptors for the Fc end of IgG, making it unlikely that they are either "natural killer" (NK) cells of cells mediating antibody-dependent cellular cytotoxicity. They may, however, be cytotoxic T lymphocytes.
Differentiation of Thy 1-bearing cells from progenitors in long-term bone marrow cultures.
Lone-term marrow cultures, established according to the technique described by Dexter, contain a colony-forming cell (CFU-T) that produces Thy 1-positive progeny after stimulation with PHA-induced conditioned medium from human leukocytes. When 10(-7) M hydrocortisone is added to the medium for the long-term cultures CFU-T can be maintained in vitro for at least 16 weeks. Cells from individual colonies lack precursors for cytotoxic lymphocytes but can provide nonspecific help required for the generation of cytotoxic lymphocytes.
Characterization of in vitro T lymphocyte colonies from normal mouse spleen cells: colonies containing cytotoxic lymphocyte precursors.
The functional activity of T cell colonies grown from normal murine spleen cells has been examined. Up to 75% of the T cell colonies contain cytotoxic lymphocyte precursors (CLP). One out of three colonies contains CLP, which can respond to a given foreign H-2 haplotype. The CLP from the T cell colonies appear identical to the CLP in lymph node tissues in their degree of cross-reactivity and requirement for accessory cells. The effector cells produced were shown to be T lymphocytes. Karyotypic analysis of the cells in colonies grown from a mixture of T6-marked and normal spleen cells indicated that individual colonies were formed from an initial small aggregate of cells. Radiation survival data indicated that the colony-forming unit contains three or fewer proliferating cells.
Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study.
Nine medical centers collaborated in a prospective randomized study to evaluate prolonged extracorporeal membrane oxygenation (ECMO) as a therapy for severe acute respiratory failure (ARF). Ninety adult patients were selected by common criteria of arterial hypoxemia and treated with either conventional mechanical ventilation (48 patients) or mechanical ventilation supplemented with partial venoarterial bypass (42 patients). Four patients in each group survived. The majority of patients suffered acute bacterial or viral pneumonia (57%). All nine patients with pulmonary embolism and six patients with posttraumatic acute respiratory failure died. The majority of patients died of progressive reduction of transpulmonary gas exchange and decreased compliance due to diffuse pulmonary inflammation, necrosis, and fibrosis. We conclude that ECMO can support respiratory gas exchange but did not increase the probability of long-term survival in patients with severe ARF.
Postoperative ulnar neuropathy.
Although compressive ulnar neuropathy developing during surgical procedures under general anesthesia has been recognized, clinical and electrophysiological features of this neuropathy have been incompletely described. During the past two years, we have seen eight patients with this complication, mainly following intra-abdominal or intrathoracic operations. Neuropathy was associated with a persistent severe deficit during a mean follow-up of 23.5 months (range, six to 96 months) after operation. Electrophysiological studies verified substantial Wallerian degeneration in the majority of patients. Clinical and electrophysiological data, as well as intraoperative findings in some patients, suggest that compression occurred at the cubital tunnel. These patients with ulnar neuropathy had a particularly poor prognosis, whether treated surgically (decompression or transposition) or medically. Prevention of ulnar nerve compression during major operations therefore assumes paramount importance.
Sporadic distal myopathy with early adult onset.
With the exception of the large series of adult-onset hereditary distal myopathy from Sweden, few cases of primary muscle disease with a definite distal predilection have been published. We report 3 sporadic cases of distal myopathy with the following features: (1) early adult onset (26 to 33 years); (2) slowly progressive weakness affecting first the distal leg muscles and later the arms; (3) marked elevation of creatine phosphokinase (more than 10 times the normal value); and (4) electromyographic and histological evidence of myopathy in distal muscles. The differential diagnosis is discussed and other reported cases are reviewed. The differences between hereditary cases reported by others and the sporadic cases reported here form the basis for a tentative subclassification of this syndrome.
Dynamic properties of partially denervated muscle.
The mechanical and electrical properties of the partially denervated first dorsal interosseous muscle were measured in 14 patients and 14 normal control subjects. The following variables were studied during isometric contraction: maximum voluntary contraction; maximum rate of rise of tension in a rapid voluntary contraction; amplitude, rate of rise, time to peak, and duration of peak of the compound muscle action potential; twitch force, maximum rate of rise, contraction time, and half-relaxation time; and tetanic (50 Hz) force, rate of rise, and tetanus/twitch ratio. The force produced during repetitive stimulation of the ulnar nerve at 10, 20, 50, and 100 impulses per second was also analyzed. The major findings were: (1) decreased load bearing (voluntary contraction, twitch, and tetanus), (2) prolonged twitch contraction times and half-relaxation times, (3) decreased tetanus/twitch ratio, and (4) preserved rate of rise of tension.
The cubital tunnel syndrome: diagnosis and precise localization.
The cubital tunnel syndrome is a subgroup of ulnar neuropathies arising at the elbow, with nerve entrapment under the aponeurosis connecting the two heads of the flexor carpi ulnaris muscle. To separate this condition more clearly from tardy ulnar palsy, the clinical and electrophysiological features of 9 patients are presented, 6 of whom had the syndrome bilaterally. There was no history of trauma and no clinical or roentgenographic evidence of joint deformity in any of the patients. In 9 of the 15 ulnar nerves, abnormal conduction was localized to the level of the cubital tunnel (1.5 to 3.5 cm distal to the medial epicondyle). The findings were confirmed intraoperatively in 7 patients and corresponded to a tight band compressing the ulnar nerve and causing narrowing at the cubital tunnel with swelling proximally. This syndrome represents a common and distinct subgroup of ulnar neuropathies at the elbow.
An attempt to define the nature of chemical diabetes using a multidimensional analysis.
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Delays in the postnatal increase of cerebral cytochrome concentrations in lead-exposed rats.
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Comments on the fluorescein excitation and emission polarization spectra in living cells.
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Fluorescence intensity resolution in flow systems.
The factor which can limit fluorescence intensity resolution in a flow cytometer of the type in which cells pass perpendicularly through a focussed laser beam depends on signal intensity. For the brightest sources (e.g. fluorescent DNA stains), the coefficient of variation (CV) is limited in our system to around 3% by stream hydrodynamics, unstable illumination intensity, nonstoichiometric staining, etc. The weakest detectable sources (e.g. fluorescent cell-surface labels) are limited in coefficient of variation by shot noise in the photomultiplier due to constant background light levels. Finally, over a fairly wide brightness range between these extremes, resolution is determined primarily by photoelectron statistical variation on the signal itself (i.e. "photon statistics"). Thus photon collection and detection efficiency (solid angle, barrier filter passband, detector quantum efficiency) become of primary importance.
Fluorescence flow analysis of lymphocyte activation using Hoechst 33342 dye.
The in vitro response of murine lymphocytes to allogeneic and mitogenic stimulation has been studied by using the nontoxic fluorescent DNA probe, Hoechst 33342, and a fluorescence flow cytometer-cell sorter. Under appropriate conditions, two peaks of fluorescent intensity, not related to cellular DNA content, can be seen. As early as 12 hr after culture set up, lymphocyte activation can be identified. It appears that Hoechst-labeled lymphocytes of higher fluorescence intensity represent those cells activated by allogeneic stimulation whereas cells obtained from the lower intensity peak are nonresponding lymphocytes.
Juvenile-onset metachromatic leukodystrophy: biochemical and electrophysiologic studies.
A 15-year-old girl with juvenile-onset metachromatic leukodystrophy (MLD) had markedly decreased leukocyte arylsulfatase A activity and low levels of leukocyte beta galactosidase and serum acid phosphatase. There was marked slowing of nerve condition velocity, and metachromasia was seen in biopsied sural nerve. Leukocyte arylsulfatase A activity was decreased in all members of the girl's family, and sural nerve action potentials were abnormal in two asymptomatic siblings. Electrophysiologic studies combined with biochemical studies may aid in the identification of presymptomatic metachromatic leukodystrophy homozygotes or asymptomatic heterozygotes.
Characterization of in vitro T-lymphocyte colonies from spleens of nude mice.
Cells residing in the spleens of nude mice that appear Thy-1 negative can give rise to Thy-1 positive colonies in an in vitro culture system. Cells from pooled colonies can provide an accessory cell required for the development of cytotoxic lymphocytes from their precursors in an in vitro mixed lymphocyte reaction. As few as 50 such colony cells produce detectable activity.
In vitro differentiation of B lymphocytes from pre-B cells.
Adult bone marrow contains both B lymphocytes and their immediate precursors, pre-B cells. These two cells differ in size and can be separated by velocity sedimentation; B cells are enriched in the subpopulation of cells sedimenting at between 2.0 and 3.5 mm/hr and pre-B cells in the subpopulation between 5.0 and 7.0 mm/hr. Incubation of pre-B cells in vitro for 4 or 5 days leads to their differentiation into functional B lymphocytes. The transition form pre-B to B appears to occur in two steps. The first step gives mitogen responsive B cells with an intermediate sedimentation velocity and the second step produces typical small, slowly sedimenting B cells. Pre-B cells can be quantified by using a limiting dilution assay and occur at a frequency of 1/60 in the subpopulation of rapidly sedimenting bone marrow cells.