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Biomedical subjects

D Griffin

Publications and source records attributed to D Griffin.

At least 55 records · Page 3Linked to original sources
PubMed1992

An intrachromosomal insertion causing 5q22 deletion and familial adenomatous polyposis coli in two generations.

We report familial adenomatous polyposis coli (FAPC) with epidermoid cysts, osteomata, and areas of congenital hypertrophy of the retinal pigment epithelium (CHRPEs) in a male patient and his maternal aunt, both of whom suffered a mild to moderate degree of mental handicap. Both had an interstitial deletion of the long arm of chromosome 5 (del(5)(q22q23.2)). Two other normal family members had the underlying direct insertion of chromosome 5(dir ins(5)(q31.3q22q23.2)). Molecular genetic and fluorescent hybridisation studies have shown that loci D5S37 and D5S98 are outside the deletion whereas loci detected by probes EF5.44 and YN5.48 are lost. As expected, the molecular analyses indicate loss of one allele at the MCC and APC loci. The APC gene is located within band 5q22. Familial direct insertions should be considered as a cause of recurrent microdeletion syndromes.

Adenomatous Polyposis Coli↗
PubMed1992

Acute myopathy during treatment of status asthmaticus with corticosteroids and steroidal muscle relaxants.

Acute myopathy in patients being treated for severe asthma has been recognized with increasing frequency since first being described in 1977. We report three patients treated for status asthmaticus who developed severe generalized weakness. Electrophysiologic studies and muscle biopsy revealed evidence of muscle destruction. Each of these patients was treated with high-dose corticosteroids and underwent prolonged neuromuscular blockade with a steroidal muscle relaxant. A review of the literature revealed 15 similar cases. We postulate that the combined effects of corticosteroids and muscle relaxants on the muscle cell may be responsible for this myopathy. Patients treated with corticosteroids and NMBs should be carefully monitored for the development of myopathy.

Acute Disease↗
PubMed1991

Differential effects of recombinant interferon alpha on constitutive and inducible cytochrome P450 isozymes in mouse liver.

The hepatic cytochrome P450 (P450)-dependent monooxygenase system is subject to regulation by a variety of xenobiotics and endogenous factors. During infection and inflammation the P450 system is usually suppressed, but the factors responsible for this phenomenon and the P450 isozymes involved have not been identified conclusively. We have studied the effects of a specific inflammatory mediator, recombinant interferon alpha, on the constitutive and inducible expression of P450 isozymes (from the CYP1A, CYP2B, and CYP2C) gene families using isozyme preferred substrates and Western blot analysis. Both increases and decreases in P450 levels occurred in response to interferon alpha. Suppression of constitutive P450 isozyme expression occurred and was shown to involve a decrease in steady-state protein expression. The induction of 7-ethoxyresorufin O-deethylase activity by 3-MC was potentiated whereas induction of 7-pentoxyresorufin- and 7-benzyloxyresorufin O-dealkylases by PB was suppressed by interferon alpha. These data demonstrate that the effects of interferon alpha on the P450-dependent monooxygenase system are complex, involving differential regulation of several isozymes. Both direct and indirect mechanisms may participate in these phenomena.

Animals↗
PubMed1991

Social density, stressors, and depression: gender differences among the black elderly.

This research examined gender differences with regard to the effects of social density and stressors upon depressive symptomatology among 600 Black elderly community residents (aged 55-85 years) of Nashville, Tennessee. The sample had more females than males and fewer married individuals. Approximately half of the males and females lived alone. Regression analyses show that poor ego and chronic medical problems were the common predictors of depression among both the males and females. Gender differences were found with regard to life events in that females tended to become more depressed as the number of events increased and as level of contact with relatives and friends decreased. Further, females with lower levels of social attachment, guidance, and reliability were more depressed. None of these social support dimensions related to depression among the males. These relationships tended to be stronger for those living alone than for those living with others.

Black or African American↗
PubMed1991

D12S56: a highly polymorphic locus on human chromosome 12q14.

A CA repeat, subcloned from a cosmid, has been assigned to chromosome 12 by use of a panel of somatic cell hybrids. The assignment was confirmed by fluorescent in situ hybridization and the site further localized to 12q14. The repeat is highly polymorphic and should be useful for genetic mapping.

Base Sequence↗
PubMed1991

Specificity of two-site immunometric assays.

The assessment of specificity in two-site immunometric assays is complex. Conventional approaches based on standard substitution with cross-reactant may yield misleading results. An 'in-house' immunoradiometric assay (IRMA) for human growth hormone (hGH) appeared free from cross-reactivity with human placental lactogen (hPL) in a single point standard substitution experiment performed by the United Kingdom External Quality Assessment Scheme (UK EQAS). However, detailed studies based on the substitution of hGH standards with hPL cross-reactant, the addition of hPL cross-reactant to hGH standards and the recovery of added hGH from endogenous cross-reactant (sera from pregnant subjects) revealed gross cross-reactivity of hPL in the hGH assay. We recommend that the validation of assay specificity should require the demonstration of quantitative recovery of a range of analyte concentrations from human sera that contain varying endogenous concentrations of cross-reactant.

Calibration↗
PubMed1991

In vitro vs in vivo corrosion analyses of two alloys.

The in vitro and in vivo corrosion characteristics of two alloys, cast Co-Cr-Mo (ASTM F75) and wrought Ni-Cr-Mo, were evaluated using electro-chemical corrosion analysis. Two in vitro electrolytic solutions were utilized, an isotonic saline solution consisting of 0.9 w/o NaCl in distilled water and an isotonic saline solution with 10 v/o sterile calf serum. The in vivo environment was created by implanting cylindrically shaped specimens of each alloy into the back muscles of New Zealand white rabbits. Cyclic anodic and cathodic polarization curves were generated for the three test conditions and subsequently were compared. Anodic curves conducted using the isotonic saline and isotonic saline plus serum electrolyte solutions were very similar to the anodic curves generated for the implanted alloy specimens for both alloys. The corrosion rates predicted from the in vitro and in vivo cathodic polarization curves were not statistically different for the three test conditions. Overall, the corrosion data generated using the in vitro environmental conditions adequately predicted the in vivo corrosion behavior of the cast Co-Cr-Mo and wrought Ni-Cr-Mo alloys.

Animals↗
PubMed1990

Bone acidic glycoprotein-75 is a major synthetic product of osteoblastic cells and localized as 75- and/or 50-kDa forms in mineralized phases of bone and growth plate and in serum.

Anti-peptide and anti-protein antisera were produced which both recognize bone acidic glycoprotein-75 (Mr = 75,000) and an apparent fragment or biosynthetic intermediate (Mr = 50,000) in calcified tissues and/or serum. A fragment-precursor relationship is suggested from the fact that closely spaced doublet polypeptides of Mr = 50,000 could be produced by proteolysis of the purified protein upon long term storage. No reactivity was detected with osteopontin, bone sialoprotein, or small bone proteoglycans. Bone acidic glycoprotein-75 represents 0.5-1% of the total radiolabeled proteins synthesized by explant cultures of neonatal calvaria or growth plate, by calvarial outgrowth cultures, and by rat osteosarcoma cells. Amounts produced by explant cultures and calvarial outgrowth cultures were similar to that for osteopontin, a major product of osteoblasts. In osteosarcoma cultures, 80% of labeled antigens were associated with the cell layer fraction wherein specific immunoprecipitation pelleted Mr = 50,000 and 75,000 sized antigens. Bone acidic glycoprotein-75 (Mr = 75,000) is enriched in 4 M guanidine HCl/0.5 EDTA extracts of neonatal rat bone and growth plate tissues, whereas largely absent from heart, lung, spleen, liver, brain, and kidney. Explant cultures of these noncalcifying tissues also synthesized bone acidic glycoprotein-75 antigen, but the quantities produced were only 5% or less that obtained with calvaria. By immunohistochemistry, antigenicity is associated with the bony shaft and calcified cartilage of long bones, but is absent from associated soft tissues. These finding demonstrate that bone acidic glycoprotein-75 is antigenically distinct, predominantly localized to calcified tissues, represents a major product of normal osteoblastic cells and may undergo a characteristic fragmentation in vivo and in vitro.

Animals↗
PubMed1990

An evaluation of a therapeutic health program for the black elderly.

This paper evaluates the effectiveness of a therapeutic health program which was offered in 1988 to the black elderly living in subsidized high-rise apartments in Nashville. The pre-program data (of 1987) indicated distinct differences in that the elderly living in the high-rises had significantly more medical problems, higher levels of depression, and smaller social support networks than those living in their own single dwelling homes. The therapeutic program included various modules such as cognitive and grief therapy, reminiscence therapy, social skills and remotivation therapy. Analyses of pre-post measures of selected variables showed that the program was effective in improving the health status of the participants. As compared to a non-treatment control group, the elderly in the experimental group showed significant improvements in depression, social network, and a sense of control over their lives. A discussion of these findings is provided.

Black or African American↗
PubMed1990

A survey of dementia carers: doctors' communications, problem behaviours and institutional care.

A survey of carers belonging to the Alzheimer's Disease and Related Disorders Society (ADARDS) had three aims: (i) to investigate the process of health professionals providing information to patients and carers: (ii) to determine the nature of problems burdening carers; and (iii) to examine factors associated with institutional placement. Carers reported on deficiencies in the provision of information and indicated their preferences as to how the information should be given. ADARDS, general practitioners and other health professionals were reportedly helpful, with each appearing to have a role in providing information about dementia. Multiple problem behaviours were reported by most carers, especially difficulties with communication, the need for constant supervision and disruption to personal life. Institutional care was most highly correlated with dependency problems, severity of dementia and a non-spouse carer. Implications include the need for training of doctors in communication and education about dementia with particular attention to management of dependency problems.

Adaptation, Psychological↗
PubMed1988

Childhood adrenoleukodystrophy. Failure of intensive immunosuppression to arrest neurologic progression.

Cyclophosphamide in a dosage of 350 to 700 mg/m2/d was administered for five to 11 days to four patients with childhood adrenoleukodystrophy (ALD) and to one patient with the adult cerebral form of the disease. The rate of neurologic progression in the four patients with childhood ALD did not differ from that of 167 untreated patients with childhood ALD surveyed previously.

Adrenoleukodystrophy↗
PubMed1988

Negative ion fast atom bombardment mass spectrometry of oligodeoxynucleotide carbamate analogs.

Oligonucleotide analogs, in which carbamate rather than phosphodiester linkages form the backbone, have been analyzed by negative ion fast atom bombardment mass spectrometry. These oligodeoxynucleotides, dimers (982.4 daltons) to 11-mers (4356.5 daltons), show intense [M - H]- ions and some degree of cleavage of the sugar-carbamate backbone structure in repeating fashion on both sides of the carbonyl groups. Sequencing of the shorter chain oligonucleotide analogs, up to six bases long, is demonstrated by complete 3' and 5' terminal sequence fragment ions. Longer chain oligomers show partial sequencing information.

Carbamates↗
PubMed1988

Serum antibodies to GM1 ganglioside in amyotrophic lateral sclerosis.

We report the presence of serum antibodies directed against GM1 ganglioside, a defined neural antigen, in many patients with amyotrophic lateral sclerosis (ALS). We examined serum from a series of patients with well-documented clinical diagnoses. Serum antibodies to GM1 ganglioside were measured using ELISA assays. Our results showed that polyclonal IgM anti-GM1 antibodies were present at dilutions of 1:25 to 1:2,000 in 42 of 74 (57%) patients with ALS. The anti-GM1 antibodies were especially frequent in patients with prominent lower motor neuron signs (41/59; 69%). Few normal controls (2/23) and motor-sensory neuropathy patients (3/27) had similar antibodies. Anti-GM1 antibodies did occur in patients with nonneural autoimmune disorders. However, the anti-GM1 antibodies in these patients tended to differ from those in ALS based on an analysis of their light chain types. Further examination of the role and spectrum of serum antiganglioside antibody activity in motor neuron syndromes is warranted.

Adult↗
PubMed1987

Epitopes of human interferon-alpha defined by the reaction of monoclonal antibodies with alpha interferons and interferon analogues.

Five monoclonal antibodies reactive with human interferon (HuIFN)-alpha 2, but not with HuIFN-alpha 1, have been analyzed for their reaction with a series of IFN analogues and hybrid IFN molecules. Using analogues containing alpha 1 or gamma substitutions, it was shown that amino acids in the 107 to 113 region are implicated in the epitopes recognized by four of the five antibodies tested. Surprisingly, two of the antibodies that did not react with [alpha 1(113 to 114)112 to 113]alpha 2 also did not react with a truncated IFN-alpha 2(4 to 155). The presence of an epitope determined by amino acids at 112 and 113 and by the amino and carboxyl ends of the molecule supports a model for IFN where the carboxyl- and amino-terminals are adjacent to the proposed reverse turn around amino acid 110 to 115. The fifth alpha 2 specific antibody whose reaction with HuIFN-alpha 2 is not affected by the above substitutions and truncations recognizes IFN or IFN hybrids that, like alpha 2, have arginine at position 120, but does not react with IFN that, like alpha 1, have lysine at position 120. Amino acids 107 to 113 and 120 lie in regions of the molecule that have high hydrophilicity and are probably structurally involved in the epitopes recognized by the antibodies. Under conditions of antibody excess, the antibodies described here inhibit binding of HuIFN-alpha 2 to both human and bovine cells.

Animals↗
PubMed1987

Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using omega-conotoxin from Conus magus venom.

The omega-conotoxins from the venom of fish-hunting cone snails are probably the most useful of presently available ligands for neuronal Ca channels from vertebrates. Two of these peptide toxins, omega-conotoxins MVIIA and MVIIB from the venom of Conus magus, were purified. The amino acid sequences show significant differences from omega-conotoxins from Conus geographus. Total synthesis of omega-conotoxin MVIIA was achieved, and biologically active radiolabeled toxin was produced by iodination. Although omega-conotoxins from C. geographus (GVIA) and C. magus (MVIIA) appear to compete for the same sites in mammalian brain, in amphibian brain the high-affinity binding of omega-conotoxin MVIIA has narrower specificity. In this system, it is demonstrated that a combination of two omega-conotoxins can be used for biochemically defining receptor subtypes and suggested that these correspond to subtypes of neuronal Ca2+ channels.

Amino Acid Sequence↗
PubMed1987

The enterohepatic circulation of methotrexate in vivo: inhibition by bile salt.

We examined the enterohepatic circulation of methotrexate (MTX) in the rat in vivo and determined the effect of the unconjugated bile salt, cholate, on the process. MTX (70 mg/kg body weight) was administered i. v. and the bile salt (1 mM) was delivered through intestinal perfusion. In the control group 38.43% +/- 4% of the administered dose of MTX appeared in bile 2 h after administration of the drug. In the bile salt-treated group 21.4% +/- 3.7% of the administered doses of MTX appeared in bile, which was significantly lower (P less than 0.01) than the proportion in the control group. The liver content of MTX was depressed by 23% in the bile salt-treated group compared with the control group. This study demonstrates, in vivo, the important role that the enterohepatic circulation plays in exposing the small intestine to toxic levels of MTX and shows that the unconjugated bile salt, cholate, inhibits the process.

Animals↗