Home healthcare. A high-technology business.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J Muller.
Explore the source record for details and available documents.
A collaborative effort to describe patients at admission led to the development of the Central Data Set, a 32-item profile of demographic and clinical variables which was used to sample 1,302 admissions across 10 hospitals in 1982. Weighted estimates indicated that this group of adult patients admitted to CNPHA-member hospitals were younger than those admitted to other private psychiatric hospitals, almost half had more than one previous psychiatric hospitalization, about one-fourth had made a previous suicide attempt, and two-thirds had engaged in psychotherapy or counseling prior to his admission. Most common diagnoses at admission were major affective disorders (36%), personality disorders (36%), substance abuse (30%), schizophrenic disorders (13%), and depressive neuroses (13%).
Explore the source record for details and available documents.
Specimens of the quadriceps femoris muscle from four infants with neonatal myotonic dystrophy had features of muscle fiber immaturity. Delayed establishment of major fiber subtypes and persistent myotubes, seen in the youngest infant, resolved in a repeated specimen obtained at the age of 4 months. Prominence of satellite cells, central nuclei, acid phosphatase activity sites, and Golgi zones diminished with age at biopsy. All four infants had type 1 fiber-size disproportion. These results substantiate the concept of delayed muscle fiber maturation in myotonic dystrophy.
We investigated the growth characteristics of a human colon carcinoma cell line, WiDr, grown in culture flasks and on chick embryonic skin (CES). WiDr cells labeled in vitro with bromodeoxyuridine (BrdU) and analyzed by combined propidium iodide/Hoechst 33258 fluorescence showed evidence of more BrdU incorporation in early S phase as compared to late S phase. When inoculated on the CES, WiDr cells multiplied and invaded the underlying skin. Morphologic examination showed that with extended culture WiDr cells on the CES undergo progressive structural organization with the development of acini and basal lamina, structures similar to those in in vivo tumors. WiDr cells were labeled with monoclonal antibody to carcinoembryonic antigen (CEA) and the brightest 2% of the population was sorted. When subsequently grown on the CES, the sorted cells formed significantly more acinar structures at 3 and 6 days of culture than an unsorted population grown for a comparable time.
A large kindred, with two brothers coming to autopsy, of a syndrome consisting of ataxia, dementia, and some Parkinsonian features is reported; inheritance appears to be autosomal dominant. Neuropathologically, there were plaques and neurofibrillary tangles in the cerebral cortex as well as some in the basal ganglia, particularly reminiscent of the plaques seen in Kuru; there was only minimal spinal cord disease (pyramidal tract field). The problems of classifying this condition--Alzheimer's disease with cerebellar involvement or other entities, such as the Gerstmann-Sträussler-Scheinker condition (1936), especially now that transmission to animals in the latter has been reported--are discussed. Some relevant theoretical considerations derived from animal work, particularly in scrapie, are also reviewed.
The possible routes of transvascular migration of leukemic cells in the liver were studied in guinea pigs with an L2C lymphoblastic cell-line inoculation leukemia. Invasion of the hepatic parenchyma theoretically can occur in three ways: Through the intact sinusoidal endothelium, utilizing either preexistent gaps (normal in the liver), or newly created pores, whether interendothelial or intraendothelial. We could not convincingly demonstrate this, but could not wholly exclude this either. After destruction or retraction of the endothelium, either on account of the remarkable sinusoidal engorgement and distension by masses of leukemic cells, or by direct assault on the endothelium by the leukemic cells. We can clearly demonstrate the former, and hold it to be the major cause of hepatic infiltration. Evidence for a direct endotheliolytic effect was not uncovered in our studies. Secondary infiltration from the portal triads. Heavy leukemic infiltration of the triads, whether from the portal or hepatic veins, or from the lymphatics, is indeed and early an consistent feature--but the infiltration of the hepatic lobule shows no peripheral, or any other zonal preference. In both portal and hepatic veins, leukemic cells transverse the endothelium through a cytoplasmic "pore", adjacent to cell junctions, without obvious damage to the endothelium.
A case of sudden, unexplained death in a 24-year-old male is presented. There were two previous spells of loss of consciousness. There was remarkable narrowing of the foramen magnum with indentation of the medulla. The atlas was partly fused with the occipital bone and a portion of abnormal bone compromised the foramen magnum from anterior reducing its anteroposterior dimensions to 16 mm (n 25-35 mm). Close clinical examination of this area in patients with acute intermittent symptomatology, or at the time of autopsy in cases of sudden unexpected death is stressed.
Intramembranous particle aggregates (presumed sites for water flow) which appear in the luminal membrane consequent to ADH treatment are derived from cytoplasmic membrane structures (now termed "aggrephores") which fuse with the luminal membrane. We have previously shown that bladders stimulated in the absence of an osmotic gradient have about twice as many aggregates and about three times as many sites of aggrephore fusion as bladders stimulated with ADH in the presence of a 175 milliosmolal gradient. The present studies show that the frequency of fused aggrephores and luminal membrane aggregates can be modified as a consequence of alterations in transmembrane water flow initiated by changing the transbladder osmotic gradient during hormone stimulation. Bladders treated with ADH for 1 hr without a gradient and then for 1 hr with a gradient had approximately 1/3 as many aggregates and fusion sites as paired bladders treated for 2 hr without a gradient. Conversely, bladders treated with ADH for 1 hr with a gradient and then for 1 hr without a gradient had approximately 2x as many aggregates and fusion sites as bladders treated for 2 hr with a gradient. In other experiments we demonstrate that the time course of hormone washout is greatly accelerated if carried out in the presence of an osmotic gradient. In paired bladders that were first stimulated with ADH for 30 min in the absence of a gradient, aggregates and fusion sites as well as osmotic water permeability determined in fixed bladders, persisted at near maximum levels for 15 min of washout in the absence of a gradient.(ABSTRACT TRUNCATED AT 250 WORDS)
In most areas of the body, arteries and veins run close together, often sharing a common connective tissue sheath. One exception to this is observed in the brain, where arteries come in from the base and veins collect over the convexity. Classically the larger blood vessels are formed by three coats: intima, media, and adventitia. Leptomeningeal vessels are further reinforced by a monolayer of pial cells. In the guinea pig, however, above the corpus callosum we found a group of blood vessels (an artery and several veins) enclosed in a common leptomeningeal sheath. The artery arises at the confluence of the anterior cerebral arteries; the veins drain into the straight sinus. The epithelial nature of the sheath is evident by the close apposition of cell membranes, the presence of junctional devices, and the existence of a basal lamina. The ultrastructural features of this epithelium are similar to those of the arachnoid-dural membrane. Whether this peculiar vascular complex has any specific function needs to be investigated further. The presence of these vessels apparently 'isolated' within a leptomeningeal subcompartment may provide a suitable model to study vascular-extravascular-cerebrospinal fluid substance exchange.
The possible routes of transvascular migration of leukemic cells were studied in guinea pigs with an L2C lymphoblastic cell-line inoculation leukemia. The leukemic infiltrates were found mostly in and around the superficial leptomeningeal veins, paralleling findings in human leukemia. Reconstructions, based on thin serial sections (Epon blocks), allowed us to conclude: (1) leukemic cells do proliferate under the vascular endothelium; (2) the endothelium when pushed away from its basement membrane degenerates and ultimately disintegrates; (3) junctions between adjacent endothelial cells tend to be preserved, even when the rest of the endothelial cytoplasm has disintegrated; (4) leukemic cells will eventually re-enter the circulation; (5) leukemic cells, either singly or in groups, cross through endothelial pores in otherwise intact endothelial cells, rather than through opened-up junctions. It is concluded that leukemic cells cross the endothelium either through endothelial pores, which they in some way engender, or through large gaps left by disintegrating endothelium, the latter possibly intravasation.
The kinetics of the dissociation reaction under acidic conditions of the dimeric pig and chicken mitochondrial malate dehydrogenases (EC 1.1.1.37) have been studied. The dissociation of the pig enzyme is completely reversible. The pK for dissociation determined by light-scattering measurements agrees within experimental error with the pK value of 5.25 measured for a tyrosine-carboxylate pair. The rate constants for the dissociation reaction and for the protonation process of this tyrosine are in close agreement. Thus, the tyrosine-carboxylate pair can be used as indicator of the dissociation reaction. The dissociation of the chicken enzyme proceeds around pH 4.5 at a much lower rate. A true equilibrium between dimer and monomers is not found, since the monomer gradually unfolds at this pH. The monomers of both enzymes, pig and chicken mitochondrial malate dehydrogenase, show the same stability towards acid. The difference in stability of the dimeric forms, therefore, must be due to an altered subunit contact area.
Explore the source record for details and available documents.
A simple device which allows the brain to be cut at any thickness in the horizontal plane or any other plane has been designed. Its use is in those cases in which during life computerized tomographic scans (CT scans) have been obtained and where display of the anatomic specimen according to the CT scan plane is required.
We studied the effects of potassium-free media on processes related to the hydro-osmotic response of toad bladder to ADH (20 mU/ml). Exposure of bladders to potassium-free media did not affect base-line osmotic water flow, but it promptly attenuated the level of osmotic water permeability induced by ADH. Both the frequency of hormonally induced intra(luminal)membrane particle aggregates (presumed sites for transmembrane water flow) and the number of luminal membrane fusion events (associated with aggregate delivery from the cytoplasm) were also reduced. Potassium-free media had no measurable effect either on cytoplasmic microtubule integrity or on mean aggregate size. Potassium repletion reversed the inhibitory effect of potassium-free media on ADH-related osmotic water permeability. For bladders fully stimulated with ADH in the presence of potassium, subsequent bathing media depletion of potassium led to an inhibition of ADH-related water flow and to reductions in membrane fusion sites and aggregates. We confirmed that the inhibitory effect of potassium-free media on ADH-induced osmotic water permeability results from serosal bathing medium potassium depletion alone and occurs at a post-cyclic AMP site. In addition, we found that ADH-stimulated water permeability was attenuated in bathing media containing a low potassium concentration (0.5 mM). The data are consistent with the view that potassium-free media or media containing low levels of potassium inhibit ADH-enhanced osmotic water permeability in toad bladder by interfering with the process of or leading to membrane fusion required for the delivery of water-conducting structures to the luminal membrane. In addition, some of our results imply that aggregates may turn over during sustained ADH stimulation.
In order to disassociate the k action of dynorphin from its other actions, seven analogs were synthesized and evaluated for pharmacologic activity in comparison with dynorphin (1-13) and dynorphin amide (1-10). Dynorphin (1-10) was modified by protecting the terminal carboxy group, incorporating thioproline at position 10 and substituting methionine for leucine at position 5. All analogs exhibited the ability to inhibit electrically-induced twitches of the guinea pig ileum and mouse vas deferens in a manner that was dose dependent and naloxone reversible. The decapeptide terminating with a pyrrolidine group showed the highest potency in the ilea and mouse vas deferens. None of the analogs showed analgetic activity by the mouse tail flick test. Binding studies using mouse brain synaptosomes showed that all seven analogs can displace the binding of tritiated dihydromorphine (DHM), ethylketocyclazocine (EKC) and D-Ala-D-Leucine enkephalin (DADL). The alterations in chemical structure affected affinity of the analogs to the opiate receptor and their pharmacologic properties differently, suggesting that different opiate subtypes may be involved.
A decrease in respiratory rate resulting from irritation of upper airways and a decrease in duration of immobility in a 'behavioural despair' swimming test occurred in mice during and following short-term inhalation exposures to some commonly used aliphatic ketones. Linear concentration-effect relationships were obtained that allowed two different median active levels (MALs) to be calculated. MALs that produced a 50% decrease in respiratory rate (RD50) were calculated as indicators of the sensory irritation potency of diisobutyl ketone, mesityl oxide, methyl amyl ketone, methyl isoamyl ketone and methyl propyl ketone. MALs that produced a 50% decrease in immobility (ID50) were determined for acetone, isophorone, mesityl oxide, methyl amyl ketone, methyl isoamyl ketone, methyl isobutyl ketone and methyl propyl ketone. The systematic determination of MALs permits classification of ketones in terms of their relative potencies for eliciting a given effect. The lowest MAL indicates the primary manifestation of toxicity, against which protection should be taken. MALs associated with such critical responses may be useful in the establishment of safe levels of occupational exposure to ketones, a conclusion supported by the linear relationship that was found to exist between MALs and occupational standards.
Correlations between molecular structure and a given biological activity have not, as yet, been widely applied to industrial toxicology. After a brief outline of the chief characteristics of the Hansch model and a definition of the selected physico-chemical parameters, this paper presents a study of the quantitative relationship between these parameters and upper-respiratory-tract irritation (determination of the RD50) for four chemical groups: ketones, alcohols, acetates and benzene derivatives.