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Biomedical subjects

L J Miller

Publications and source records attributed to L J Miller.

At least 145 records · Page 8Linked to original sources
PubMed1992

Binding of a phenethyl ester analogue of cholecystokinin to the solubilized pancreatic cholecystokinin receptor: use in ligand-affinity chromatography.

Pancreatic acinar cells have both high and low affinity receptors for cholecystokinin (CCK), yet their membranes appear to possess only a single class of binding sites. Recently, gallbladder membrane CCK receptors were shown to undergo inter-conversion between two affinity states dependent on G protein coupling. Keys for that observation were the differential binding affinities of CCK and a phenethyl ester analogue of CCK (OPE), with the high affinity state binding CCK with higher affinity than OPE, and the low affinity state binding OPE with higher affinity than CCK. Here, we performed analogous experiments using these ligands and both pancreatic membranes and a solubilized preparation. Both preparations were found to have only single affinity states of this receptor. However, the state on membranes had a higher affinity for CCK than for OPE, and that on the solubilized preparation had a higher affinity for OPE than for CCK. This supports the hypothesis that the ternary complex of ligand-receptor-G protein found in membranes represents the high affinity state of this receptor, while the uncoupled form of this receptor after solubilization represents its low affinity state. The high affinity of OPE for the solubilized receptor can be utilized in a purification strategy to follow receptor-bearing fractions and to provide an efficient and specific affinity-binding step.

Animals↗
PubMed1992

Comprehensive care of pregnant mentally ill women.

Since the onset of deinstitutionalization, there has been an unanticipated and dramatic increase in pregnancies among women with chronic mental illness, with no specific planning for how to address the unique clinical needs of this high-risk population. Shortcomings in delivering care to mentally ill women within general health care systems are reviewed, including failure to assist with family planning, failure to observe worsening mental health during pregnancy, inadequate planning for child custody, lack of access to services, and omitted pelvic examinations. Necessary components of a system to provide comprehensive and coordinated care for pregnant mentally ill women are described. These include assessment of adaptation to pregnancy and competency to care for an infant, somatic and psychotherapeutic treatment, parenting skills training, family planning services, outreach, and close liaison with obstetric services. A Chicago-based collaborative program is described as an example of providing comprehensive, specialized care with limited financial resources.

Chicago↗
PubMed1992

The Zollinger-Ellison syndrome. A collective surgical experience.

A retrospective study of 90 surgically treated patients with the Zollinger-Ellison syndrome seen from 1958 through 1990 was performed. Fifteen patients had Zollinger-Ellison syndrome as a manifestation of multiple endocrine neoplasia type I. Preoperative tumor localization was positive in 46% of 54 patients studied. Gastrinomas were identified in 66% of patients, 38% of the tumors being malignant. Postoperative eugastrinemia was achieved in 11% of patients after a variety of surgical procedures. Exploratory laparotomy provides the only chance for cure and identifies the significant prognostic factors associated with long-term patient survival: small tumor size, extrapancreatic primary, and absence of tumor metastases.

Adolescent↗
PubMed1992

Ifosfamide-induced neurotoxicity: a case report and review of the literature.

OBJECTIVE: To review published abstracts, journal articles, and case reports for evidence of ifosfamide-induced neurotoxicity in both adult and pediatric populations. DATA SOURCES: Peer-reviewed journal articles (October 1985 through August 1990) obtained through a computer literature search, with subsequent bibliography scanning. STUDY SELECTION: We identified 34 reports that specifically addressed neurotoxicity related to ifosfamide therapy. By consensus of the authors, 8 of these reports were excluded due to a small study population, duplication of age of data. DATA EXTRACTION: Studies were assessed by the first author and verified by the second author. Several colleagues also contributed to the analysis. DATA ANALYSIS: Risk factors and mechanisms behind this potentially fatal neurotoxic reaction remain speculative and, in some cases, contradictory. The predictive capability of a published nomogram is restricted by differences in dosage regimens and encephalopathic classifications. Currently, the best prevention against neurotoxicity is little or no use of concurrent medications that have central nervous system effects. CONCLUSIONS: Further studies should address the influence of other nephrotoxic agents (e.g., cisplatin, aminoglycosides) on the incidence of ifosfamide-induced neurotoxicity.

Adult↗
PubMed1992

The role of the histotechnician in Mohs surgery.

Critical elements of Mohs micrographic surgery are performed by the histotechnician in the frozen section laboratory. This article provides an overview of the essential role of the histotechnician as a member of the micrographic surgical team.

Histocytological Preparation Techniques↗
PubMed1991

Agonist-regulated phosphorylation of the pancreatic cholecystokinin receptor.

The present study was undertaken to determine if the cholecystokinin (CCK) receptor may be phosphorylated, and to gain insight into its regulation. For this, the ATP pool of rat pancreatic acini was prelabeled with 32P, and the cells were stimulated with various secretagogues. CCK receptors from treated cells were enriched by sequential fractionation to produce plasmalemma, and subsequent solubilization and lectin-affinity chromatography. This protocol detected a phosphorylated Mr = 85,000-95,000 plasma membrane glycoprotein with features similar to the CCK receptor. Phosphorylation of this protein occurred rapidly (less than 2 min) and in a concentration-dependent manner in response to CCK, and was inhibited by the CCK receptor antagonist L-364,718. Further evidence that this represented the CCK receptor included comigration of phosphorylated and CCK radioligand affinity-labeled proteins on sodium dodecyl sulfate-polyacrylamide gels, both in native forms and after endoglycosidase F deglycosylation, and the specific adsorption of the phosphoprotein to a CCK analogue affinity resin. Phosphorylation occurred predominantly on serine residues of the receptor protein. Phosphorylation of this protein was also enhanced in response to other secretagogues which, like CCK, stimulate a cascade leading to protein kinase C activation, and in response to direct activation of this enzyme by 12-O-tetradecanoylphorbol 13-acetate. Thus, the pancreatic CCK receptor is phosphorylated in a regulated manner, in response to both homologous and heterologous secretagogues, and to protein kinase C activation.

Adenosine Triphosphate↗
PubMed1991

Use of photoaffinity probes containing poly(ethylene glycol) spacers for topographical mapping of the cholecystokinin receptor complex.

To further define the structure of the pancreatic cholecystokinin (CCK) receptor and the topographical distance relationships between its subunits, we developed a series of monofunctional photoaffinity probes in which a fixed receptor-binding domain was separated from a photolabile nitrophenylacetamido group by defined lengths of a flexible spacer. The well-characterized CCK receptor radioligand 125I-D-Tyr-Gly-[(Nle28,31)CCK-26-33] provided the receptor-binding component of the probes, while the polymer poly(ethylene glycol) (2, 4, 7, and 10 monomer units long) was used as the spacer. The patterns of affinity labeling of rat pancreatic plasma membranes were examined as a function of spacer length. This ranged from 7.3 to 16.2 A, as calculated by root-mean-square end-to-end distances and validated experimentally by time-resolved fluorescence resonance energy transfer measurements. All probes in the series specifically labeled the Mr = 85,000-95,000 glycoprotein with Mr = 42,000 core, which has been proposed to contain the hormone recognition site. In addition, when the spacer length reached 16.2 A, membrane proteins of Mr = 80,000 and Mr = 40,000 were specifically labeled. The product of endo-beta-N-acetylglucosaminidase F digestion of the Mr = 80,000 protein was Mr = 65,000, similar to a protein previously identified in affinity labeling experiments using a CCK-33-based probe. These observations are consistent with the Mr = 85,000-95,000 pancreatic protein representing the hormone-binding subunit of the CCK receptor, while proteins of Mr = 80,000 and Mr = 40,000 may represent noncovalently associated subunits sited within 16.2 A of the binding domain.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1991

Enteric neuronal autoantibodies in pseudoobstruction with small-cell lung carcinoma.

Severe gastrointestinal dysmotility is a newly recognized paraneoplastic syndrome that occurs with small-cell lung carcinoma. Thirty-four patients with small-cell carcinoma, of whom 5 had chronic intestinal pseudoobstruction and 29 had no digestive symptoms, were studied serologically. Four of the 5 patients with gut dysmotility had immunoglobulin G antibodies reactive with neurons of the myenteric and submucosal plexuses of jejunum and stomach in an indirect immunofluorescence assay. Antibodies of this type were not found in any of the 29 patients who had no gut dysmotility, nor were they found in patients with chronic idiopathic intestinal pseudoobstruction (n = 8), ovarian cancer (n = 20), or epilepsy (n = 4) or in normal subjects (n = 9). In 4 of the patients with paraneoplastic pseudoobstruction, antibodies in highly diluted serum (1:4000-1:8000) bound selectively to nuclei and cytoplasm of neuronal elements in the gut. This novel autoantibody activity suggests that intestinal pseudoobstruction occurring in patients with small-cell carcinoma may have an autoimmune basis. From a clinical standpoint, serological testing offers a simple means for determining which patients with gut dysmotility syndromes may have associated small-cell carcinoma, thereby enabling earlier diagnosis and treatment of the tumor.

Aged↗
PubMed1991

Abnormal gallbladder motility in irritable bowel syndrome: evidence for target-organ defect.

We have described previously that the gallbladder responds abnormally to infusions of cholecystokinin octapeptide (CCK-8) in patients with irritable bowel syndrome (IBS). To confirm these results and to examine the possible mechanisms, patients with IBS and predominant symptoms of diarrhea or constipation were compared with matched controls. During infusions of CCK-8 at one of three doses, the response of the gallbladder was measured ultrasonographically. The levels of CCK-8 reached in the peripheral circulation and degradation of the peptide in vitro and in vivo were used to evaluate metabolism of cholecystokinin. We confirmed that the gallbladders of patients with IBS responded abnormally to CCK-8; however, the differences were not due to any prereceptor event. Instead, this abnormality in IBS must be explained by an atypical response at the level of the target tissues.

Adult↗
PubMed1991

Clinical strategies for the use of psychotropic drugs during pregnancy.

The treatment of major psychiatric disorders during pregnancy is becoming an increasing challenge for the clinician as fertility rates rise among mentally ill women. When prescribing psychotropic medication, the risk/benefit analysis comes to include the risks of the medication to the fetus, special risks to the mother because of the pregnant state, and the risks to both mother and fetus of the untreated psychiatric disorder. This article will review what is known about the risks to mother and fetus of antipsychotic, antidepressant, anxiolytic, mood stabilizing and antiparkinsonian agents, and will present treatment strategies designed to minimize those risks.

Anti-Anxiety Agents↗
PubMed1991

The gall bladder cholecystokinin receptor exists in two guanine nucleotide-binding protein-regulated affinity states.

To study proximal events in cholecystokinin (CCK) action on bovine gall bladder smooth muscle, we used the hormone analogue D-Tyr-Gly-[(N1e28,31)CCK-26-32]-phenethyl ester (OPE), which has unique biological properties. This fully efficacious agonist differs from native CCK by not expressing supramaximal inhibition of cell shortening, yet it clearly interacts with the same receptor molecule. This was demonstrated in binding and affinity labeling studies, where both peptides label the same Mr 70,000-85,000 protein and both fully compete for binding of the other ligand. Further, its relatively high affinity for the low affinity CCK receptor permits the clear demonstration of two affinity states of a CCK receptor on a membrane preparation and makes possible evaluation of the molecular basis of these affinity states and their regulation. Analysis of homologous and heterologous binding curves performed with both CCK and OPE peptides and radioligands demonstrated the presence of two affinity states, with CCK being able to distinguish them (Kd1 = 0.48 +/- 0.04 nM and Kd2 = 56.5 +/- 7.4 nM) and OPE recognizing them equally (Kd1 = 0.94 +/- 0.31 nM and Kd2 = 0.96 +/- 0.23 nM). In the presence of nonhydrolyzable GTP analogues, there was a shift in distribution of receptors toward the low affinity state, with the total number of receptors and their absolute affinities for each peptide remaining constant. Thus, the gall bladder CCK receptor is a single molecule capable of assuming two interconvertible affinity states, regulated by a guanine nucleotide-binding protein. Two full agonists are capable of interacting with this molecule to yield different biological responses via different molecular events.

Animals↗
PubMed1991

3'-Phosphoadenosine-5'-phosphosulfate: photoaffinity ligand for sulfotransferase enzymes.

Sulfation is an important pathway in the biotransformation of many drugs, xenobiotic compounds, neurotransmitters, and hormones. The sulfate donor for these reactions is 3'-phosphoadenosine-5'-phosphosulfate (PAPS). We set out to determine whether PAPS might serve as a photoaffinity ligand for sulfotransferase enzymes. UV irradiation of [35S]PAPS with partially purified human liver thermostable (TS) phenol sulfotransferase (PST) radioactively labeled a protein with a molecular mass of 35 kDa, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Photoaffinity labeling of TS PST with [35S] PAPS did not require the presence of a phenolic substrate but rather was inhibited by p-nitrophenol, a sulfate acceptor substrate for TS PST. Inhibitors of TS PST enzymatic activity, including 3'-phosphoadenosine-5'-phosphate, ATP, ADP, and 2,6-dichloro-4-nitrophenol, also inhibited photoaffinity labeling of the 35-kDa protein with [35S]PAPS, in a concentration-dependent fashion, with IC50 values of 14 microM, 2.1 mM, 7.7 mM, and 91 microM, respectively. The 35-kDa protein that was radioactively labeled by [35S]PAPS in the presence of UV light coeluted with TS PST enzymatic activity during gel filtration high performance liquid chromatography. [35S]PAPS was then used to photoaffinity label another sulfotransferase enzyme, the thermolabile (TL) form of PST partially purified from human liver. Therefore, [35S]PAPS appears to be a photoaffinity ligand that could be used to study a variety of PAPS-dependent sulfotransferases. Photoaffinity labeling of TS and TL PST, as well as other PAPS-dependent sulfotransferases, should enhance our ability to purify this important group of enzymes and to determine amino acid sequences at or near their active sites.

Adenosine Diphosphate↗
PubMed1990

Gallbladder CCK receptors: species differences in glycosylation of similar protein cores.

Receptors for cholecystokinin (CCK) on gallbladder muscularis smooth muscle have different apparent sizes in man (Mr = 85,000-95,000) and cow (Mr = 70,000-85,000). In this work, these receptors were demonstrated to represent N-linked complex glycoproteins with Mr = 43,000 protein cores, based on lectin-affinity chromatography and the deglycosylation of bands affinity labeled with 125I-D-Tyr-Gly-[(Nle28,31, pNO2-Phe33)CCK-26-33] using neuraminidase, O-glycanase and endoglycosidases H and F. Similarities in the core proteins were further demonstrated by Staphylococcus aureus V8 protease peptide mapping, in which both proteins yielded similar fragment patterns. Thus, gallbladder CCK receptors present in man and cow are both N-linked complex glycoproteins, with different carbohydrate domains and similar protein cores.

Affinity Labels↗