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Biomedical subjects

H Miller

Publications and source records attributed to H Miller.

At least 145 records · Page 8Linked to original sources

The role of retinal pigment epithelium in the involution of subretinal neovascularization.

The extravascular milieu around laser-induced experimental subretinal neovascularization (SRN) was studied during the evolution of the neovascular membrane from its early leaky stage to its late involuted stage. When the first signs of visible leakage appeared on angiography, newly formed vessels were spread in the subretinal space around the break in Bruch's membrane, fluid was accumulating in the subretinal space, and retinal pigment epithelial (RPE) cells were proliferating in a papillary pattern around the newly formed vessels; the RPE proliferation began with the undamaged cells at the edges of the laser injury. With further maturation, the RPE continued to envelope the subretinal vessels. This RPE proliferation was associated with the disappearance of fluid between the enveloped vessels and the sensory retina, and the gradual cessation of fluorescein leakage during angiography. At the end of the involution process, when the neovascular membrane no longer demonstrated any leakage, the subretinal vessels were found to be tightly enveloped by RPE cells, and no fluid separated them from the sensory retina. The authors' results suggest that involution of the neovascular membrane with maturation, as demonstrated by the cessation of visible fluorescein leakage, is the result of RPE proliferation that tightly envelopes the newly formed vessels and probably resorbs the previously accumulated subretinal fluid, as well as preventing its further accumulation in the subretinal space.

Animals↗

On the role of protein kinase subunits in the control of eukaryotic gene expression.

Transcriptional regulation by cAMP has been demonstrated for several eukaryotic genes; however, the identity of the protein kinase subunit involved has been a source of debate. Based on homologies with the procaryotic cAMP-binding catabolite activator protein, a recent hypothesis has invoked the regulatory protein RII as the mediator. The evidence currently available on the effects of microinjected kinase subunits suggests, however, that the catalytic subunit is the active factor. Moreover, the proposed homologies between the catabolite activator protein and RII are difficult to reconcile with its proposed mediatory role. We suggest as an alternative hypothesis that a phosphoprotein other than RII may mediate the effects of cAMP on eukaryotic gene expression.

Cyclic AMP↗

A case of invasive thymoma associated with myasthenia gravis, myositis and demyelinating neuropathy.

A 56 year old male presented after 2 months of muscle stiffness, pain and palpable lumps. Biopsy confirmed the presence of myositis. Myasthenia gravis and peripheral neuropathy became clinically apparent within days of commencing corticosteroid therapy. 4 months later, at operation, a locally invasive thymoma was found. This combination of features has not previously been described.

Demyelinating Diseases↗

Experimental vitreous syneresis.

Perfluoropropane gas was injected into the vitreous body of a primate eye. Clinical and morphologic studies revealed that the gas bubble created a large cavity within the vitreous. The cavity that subsequently filled with viscous liquid was completely enveloped by vitreous gel, thus simulating the clinical condition known as vitreous syneresis. The shell of residual vitreous, which was much thicker inferiorly and behind the lens than superiorly, seemed to be an intact and continuous layer. In spite of the extensive syneresis, posterior vitreous detachment failed to develop. Our findings suggest that a vitreous cavity, voluminous as it may be, is not sufficient to cause posterior vitreous detachment in the primate eye.

Animals↗

Insulin or increased concentration of zinc in liver, kidney or muscle does not alter the phosphoglucomutase activity in vivo.

Injection of insulin into mice and rabbit has been reported to convert the latent form of phosphoglucomutase (E X Zn) to an active form (E X Mg) without any net increase in the protein associated with this enzyme (Hashimoto et al., Biochem. Biophys. Res. Commun., 27 (1967) 369 and Peck et al., J. Biol. Chem. 242 (1971) 1160). Because the injection of Cd in rats causes a 2-fold increase in Zn concentration in the liver, it appeared that such treatment in mice would increase the concentration of the latent enzyme and thereby enhance the insulin induced activation of the enzyme. The results however show that insulin or Cd treatment, alone or in combination do not alter the concentrations of the 2 forms of enzyme in liver, kidney or muscle of normal or fasted mice. In all instances the conversion of the latent enzyme to its activated form required preincubation with a chelating agent. Fractionation of the tissue homogenates showed that upon Cd injection the concentration of Zn in the fractions of Mr less and 1000 increased 6-fold in liver and 3-fold in kidney, that in muscle remained unchanged.

Animals↗

Disseminated talc granulomatosis. An unusual finding in a patient with acquired immunodeficiency syndrome and fatal cytomegalovirus infection.

The association of disseminated magnesium silicate talc granulomatosis and acquired immunodeficiency syndrome is reported in a male homosexual who used intravenous drugs and who died of overwhelming cytomegalovirus (CMV) infection. Autopsy findings included widespread deposition of talc crystals in the lungs, liver, lymph nodes, bone marrow, and spleen. Typical CMV inclusions were seen in the lungs, kidneys, adrenal glands, gastrointestinal tract, and right eye. There was no evidence of malignancy. Analysis of peripheral blood neutrophil function revealed impaired chemotaxis and chemokinesis, but opsonophagocytosis had remained normal. The CMV infection in the small bowel was extensive and resulted in severe destruction of the muscularis propria and neural plexi, leading to marked dilatation and persistent diarrhea. The terminal course was marked by intractable hypotension, pneumonitis, and malnutrition, which could be attributed respectively to CMV involvement of the adrenal glands, lungs, and small bowel. The etiology and possible role of systemic talc granulomatosis in the development of immunosuppressive illness is reported herein.

Acquired Immunodeficiency Syndrome↗

Monoclonal antibodies to phenobarbital-induced rat liver cytochrome P-450.

Somatic cell hybrids were made between mouse myeloma cells and spleen cells derived from BALB/c female mice immunized with purified phenobarbital-induced rat liver cytochrome P-450 (PB-P-450). Hybridomas were selected in HAT medium, and the monoclonal antibodies (MAbs) produced were screened for binding to the PB-P-450 by radioimmunoassay, for immunoprecipitation of the PB-P-450, and for inhibition of PB-P-450-catalyzed enzyme activity. In two experiments, MAbs of the IgM and IgG1 were produced that bound and, in certain cases, precipitated PB-P-450. None of these MAbs, however, inhibited the PB-P-450-dependent aryl hydrocarbon hydroxylase (AHH) activity. In two other experiments, MAbs to PB-P-450 were produced that bound, precipitated and, in several cases, strongly or completely inhibited the AHH and 7-ethoxycoumarin deethylase (ECD) activities PB-P-450. These MAbs showed no activity toward the purified 3-methylcholanthrene-induced cytochrome P-450 (MC-P-450), beta-naphthoflavone-induced cytochrome P-450 (BNF-P-450) or pregnenolone 16-alpha-carbonitrile-induced cytochrome P-450 (PCN-P-450) in respect to RIA determined binding, immunoprecipitation, or inhibition of AHH activity. One of the monoclonal antibodies, MAb 2-66-3, inhibited the AHH activity of liver microsomes from PB-treated rats by 43% but did not inhibit the AHH activity of liver microsomes from control, BNF-, or MC-treated rats. The MAb 2-66-3 also inhibited ECD in microsomes from PB-treated rats by 22%. The MAb 2-66-3 showed high cross-reactivity for binding, immuno-precipitation and inhibition of enzyme activity of PB-induced cytochrome P-450 from rabbit liver (PB-P-450LM2). Two other MAbs, 4-7-1 and 4-29-5, completely inhibited the AHH of the purified PB-P-450. MAbs to different cytochromes P-450 will be of extraordinary usefulness for a variety of studies including phenotyping of individuals, species, and tissues and for the genetic analysis of P-450s as well as for the direct assay, purification, and structure determination of various cytochromes P-450.

Animals↗

Intravitreal expanding gas bubble. A morphologic study in the rabbit eye.

The morphologic changes induced by an expanding bubble of perfluoropropane (C3F8) gas in the vitreous body have been studied in the rabbit eye by dissecting microscopy and scanning and transmission electron microscopy. Initial expansion of the gas displaces water from the vitreous; the remaining vitreous forms a compressed layer on the retinal surface. Subsequent absorption and contraction of the gas bubble is associated with gradual detachment of the compressed vitreous from the retina. Eventually, vitreous detachment is complete, except for residual attachments posteriorly to the medullary rays and anteriorly to the ciliary processes. The plane of vitreous separation is predominantly at the anatomic vitreoretinal junction, although scattered islands of outer cortical vitreous are found on the surface of the retina.

Animals↗

Extensive endocardial mapping during sinus rhythm and ventricular tachycardia in a patient with arrhythmogenic right ventricular dysplasia.

A 38 year old man with arrhythmogenic right ventricular dysplasia underwent electrophysiologic study with extensive endocardial mapping of the right ventricle. During sinus rhythm, markedly reduced amplitude with or without prolonged duration was noted in multiple electrograms of the right ventricle. Delayed activation of the right ventricular outflow tract electrogram was present. Two clinical types of ventricular tachycardia with a left bundle branch block configuration and either an inferior or a superior axis were induced by ventricular stimulation. Endocardial activation sequence during the tachycardias suggested that the tachycardia with an inferior axis originated near the infundibulum, while that with a superior axis originated near the midinferior area of the right ventricle. Both areas have been previously shown to be frequently impaired in right ventricular dysplasia.

Adult↗

Comparative in vitro activities of teichomycin and vancomycin alone and in combination with rifampin and aminoglycosides against staphylococci and enterococci.

The activity of teichomycin A2 was compared with that of vancomycin in vitro against clinical isolates of staphylococci and enterococci. Teichomycin A2 was more active than vancomycin active against all isolates tested. Synergistic studies also demonstrated that teichomycin A2 combined with rifampin is more active than vancomycin combined with rifampin against Staphylococcus aureus and Staphylococcus epidermidis isolates. Teichomycin A2, either singly or in combination with an aminoglycoside, was more active against Streptococcus faecalis isolates.

Aminoglycosides↗

Phenotyping cytochromes P450 with monoclonal antibodies.

Monoclonal antibodies (MAbs) to cytochrome P-450 isozymes can be used to phenotype tissues for epitope-specific cytochrome P-450 content. MAbs that inhibit specific cytochrome P-450 dependent drug or carcinogen reactions are useful tools for quantitative measurement of the individual or classes of cytochromes P-450 that catalyze these reactions. This method has been applied successfully to animal as well as human tissues. Radioimmunoassays based on MAbs have been developed and provide a rapid and efficient means for detecting cytochromes P-450 independent of functional enzyme activity. In addition, MAbs coupled to a Sepharose support can be used to immunopurify cytochromes P-450 in a procedure that is more rapid and efficient than conventional purification schemes. MAbs add a new dimension to analyses of cytochrome P-450 multiplicity and will find numerous applications in elucidation of the relationship between cytochrome P-450 phenotype and carcinogen or drug metabolism.

Animals↗

Diabetic neovascularization: permeability and ultrastructure.

The permeability of newly formed blood vessels in proliferative diabetic retinopathy at different stages of development was correlated with their ultrastructural features. The young proliferating vessels were much more permeable to fluorescein than were the older vessels. Transmission electron microscopy revealed that the blood vessels within the young intravitreal proliferating fronds had intermediate interendothelial junctions, whereas the blood vessels within the old neovascular preretinal membranes had tight interendothelial junctions of the macula occludens type. Fenestrations were observed only rarely in the endothelial wall of either the young or the older proliferating vessels. We conclude that the principal route of fluorescein leakage from the newly formed blood vessels in proliferative diabetic retinopathy is via the interendothelial clefts.

Adult↗