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Biomedical subjects

J Collins

Publications and source records attributed to J Collins.

At least 307 records · Page 17Linked to original sources
PubMed1990

Bile acid profiles in peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.

Fast atom bombardment mass spectrometry and gas chromatography-mass spectrometry were used to analyze bile acids in the body fluids of an infant (L.C.) whose liver contained no immunoreactive peroxisomal 3-oxoacyl-CoA thiolase. The profiles were compared with those of six patients with undetectable peroxisomes (Zellweger syndrome) and two siblings (N.B. and I.B.) whose defect of peroxisomal beta-oxidation could not be localized by morphological studies of peroxisomes or by immunoblotting of peroxisomal beta-oxidation proteins. 3 alpha, 7 alpha, 12 alpha-Trihydroxy-5 beta-cholestan-26-oic acid (THCA) was present in bile and plasma of all patients. However, bile from L.C., N.B. and I.B. contained unconjugated varanic acid (3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestan-26-oic acid) as the major C27 bile acid, whereas bile from Zellweger patients contained only small amounts of varanic acid. In the bile from L.C. two isomers of varanic acid were present; in the bile from N.B. and I.B. a single isomer predominated. L.C., N.B., and I.B. all produced bile containing small amounts of (24E)-3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-en-26-oic acid [( 24E]-delta 24-THCA), its [24Z]- isomer, 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-23-en-26-oic acid and 3 alpha, 7 alpha, 12 alpha-trihydroxy-27-nor-5 beta-cholestan-24-one. The results provide evidence for peroxisomal pathways for cholic acid synthesis in man via THCA, delta 24-THCA and varanic acid and show that bile acid analyses can be used to diagnose peroxisomal thiolase deficiency.

Acetyl-CoA C-Acyltransferase↗
PubMed1990

Supplementary iodine fails to reverse hypothyroidism in adolescents and adults with endemic cretinism.

The efficacy of supplemental iodine in correcting hypothyroidism in adults and older children with endemic myxedematous cretinism is not known. To investigate this issue we administered im iodized oil (1.5 mL) to 28 hypothyroid endemic cretins (TSH, greater than 5 mIU/L) from western China, aged 14-52 yr (mean = 29 SD = 11 yr). Clinical examination, intelligence testing (Hiskey Nebraska Test of Learning Aptitude and the Griffiths Mental Development Scales), and thyroid function tests were performed before and 6 months after iodine supplementation. We found that signs of thyroid hormone deficiency, dwarfism, and delayed sexual maturity persisted after iodine supplementation. Further, mental disability and other clinical features of neurological damage were not altered by treatment. The mean serum concentration of total T4 before treatment was 75 nmol/L (SD = 40) and fell after iodized oil administration to 56 nmol/L (SD = 29; P less than 0.001). Mean serum levels of TSH before and after iodine showed a paradoxical fall [85 mIU/L (SD = 102) and 46 mIU/L (SD = 46), respectively]. Serum TSH levels decreased into the normal range (less than 5 mIU/L) in only 1 of 28 patients (4%). We conclude that iodine supplementation does not reverse thyroid hormone deficiency or its sequelae in adolescents and adults with endemic myxedematous cretinism. Iodized oil in this age group of patients with endemic cretinism does not appear to be beneficial and should be used with caution.

Adolescent↗
PubMed1990

Serum osteocalcin measurements in prostate carcinoma patients with skeletal deposits shown by bone scintigram: comparison with serum PSA/PAP measurements.

The correlation of technetium-99m-HMDP bone scintigraphic findings, serum osteocalcin as a measure of bone turnover and prostate-specific antigen (PSA) and/or prostate acid phosphatase (PAP) was determined in 19 men with bone metastasis due to prostatic carcinoma. Six of the 19 patients with metastases on bone scan showed elevation of osteocalcin. These patients had extensive metastatic disease. All 19 men with positive bone scans had high serum PSA and/or PAP levels. Serum osteocalcin measurement is less sensitive to detection of bone deposits than PSA/PAP measurements (p less than 0.0008).

Acid Phosphatase↗
PubMed1990

Subcellular changes of rat myocardium after treatment with amiodarone or desethylamiodarone, studied with electron microscopy.

Amiodarone, an antiarrhythmic agent, has proven to be unique in its capability to control arrhythmias unresponsive to conventional drugs. However, its association with many undesirable side effects after chronic usage has become just as clear. Chronic clinical toxicity with amiodarone is associated with intracellular lamellar or myelinoid inclusion bodies (onionoid bodies or corpora cepiformia) in various organs (i.e. skin, cornea, lung, liver, and lymph nodes). Previous study has demonstrated formation of these inclusion bodies in canine myocardium following multiple doses of amiodarone. The present study was designed to develop a more convenient animal model, and to measure the concentration of amiodarone, as well as desethylamiodarone (its major metabolite) in this rodent model. The direct role of desethylamiodarone in formation of lamellar inclusion bodies in rat myocardium was also investigated. Amiodarone (50 mg/kg) or desethylamiodarone (25 mg/kg) was injected intraperitoneally daily for a period of 14 days. Myocardial sections revealed the presence of lamellar inclusion bodies, round or oval in appearance, in the form of laminated or concentrically arranged membranes after either amiodarone or desethylamiodarone treatment. This is the first reference to the induction of these myelinoid inclusion bodies with desethylamiodarone. Myocardial tissue concentrations of amiodarone and desethylamiodarone exceeding plasma concentrations were found in the present study and indicate the capability of these compounds to easily distribute and accumulate in the myocardium.

Amiodarone↗
PubMed1990

A pilot study of intralymphatic interleukin-2. II. Clinical and biological effects.

Interleukin-2 (recombinant methionyl human interleukin-2 alanine 125; IL-2) was administered intralymphatically to 12 patients with advanced cancer in a phase I trial. Doses were administered once a week for 6 weeks in a dosage escalation schedule; patients were entered in four groups at successively higher starting dosages. Toxicity occurred in a profile similar to that seen with intravenous IL-2. The maximum tolerated dose with this route/schedule was 275,000 units/kg, a figure not higher than expected with intravenous administration. T1/2 alpha was prolonged to 54 min from the 13 min figure we obtained with IL-2 given intravenously. Granulocytosis and eosinophilia were seen, along with lymphocytosis following initial lymphopenia. Anti-IL-2 antibodies were seen in 42% of patients (compared to 16% with this agent given intravenously), suggesting increased immunogenicity of this route/schedule. No clinical response was achieved. Immunologic effects will be reported separately but are summarized.

Adolescent↗
PubMed1990

Human leukocyte elastase inhibitors: designed variants of human pancreatic secretory trypsin inhibitor (hPSTI).

Variants of human secretory trypsin inhibitor were constructed with the aim of producing inhibitors specific for human leukocyte elastase. Models of the hPSTI/HLE and hPSTI/chymotrypsin complexes were generated by computer aided protein design and used to plan better HLE inhibitors. This resulted in the production of the strongest and most specific inhibitors of HLE known.

Animals↗
PubMed1989

Cloning, sequencing and expression of the L-2-hydroxyisocaproate dehydrogenase-encoding gene of Lactobacillus confusus in Escherichia coli.

The gene (L-HicDH) encoding L-2-hydroxyisocaproate dehydrogenase (L-HicDH) from Lactobacillus confusus was cloned in Escherichia coli. A 69-mer oligodeoxyribonucleotide probe, derived to be complementary to the N-terminal amino acid (aa) coding sequence, was used for screening. The complete nucleotide (nt) sequence of the L-HicDH gene was determined. The 5'-end of the mRNA was mapped by primer extension and the promoter identified. Downstream from the L-HicDH gene is a typical Rho-independent terminator. The aa sequence of L-HicDH, deduced from the nt sequence, has an overall similarity of 30% to the aa sequence of L-lactate dehydrogenase (L-LDH) from Lactobacillus casei. The aa residues involved in binding of coenzyme and substrate are highly conserved in L-HicDH with respect to prokaryotic and eukaryotic L-LDHs. The L-HicDH gene could be expressed under control of phage lambda 'Leftward' and 'rightward' promoters in E. coli up to 35% of total cell protein. The enzyme produced under these conditions exhibits full specific activity and is found exclusively in soluble form.

Alcohol Oxidoreductases↗
PubMed1989

Cloning, sequencing and expression in Escherichia coli of the D-2-hydroxyisocaproate dehydrogenase gene of Lactobacillus casei.

D-2-Hydroxyisocaproic acid dehydrogenase (D-HicDH) from Lactobacillus casei was purified and partially sequenced. A 65-mer oligodeoxyribonucleotide probe corresponding to the N-terminal 23 amino acids was synthesized and a physical map was made of the genomic region which hybridized most strongly. A strongly hybridising restriction fragment was highly purified and eventually cloned at low frequency in pBR322. The original clones spontaneously produced D-HicDH at about 0.05% of total protein and showed viability problems in that 10- to 12-h growth-lag periods occurred after diluting stationary cultures into fresh medium. Subcloning into pGEM3 plasmids for sequencing with concomitant ExoIII deletion led to clones which no longer exhibited the growth inhibition characteristics but now made D-HicDH as 3 to 5% of total protein. Subcloning downstream from a double PL PR promoter in plasmid pJLA601 gave a highly inducible clone that builds large inclusion bodies of largely denatured D-HicDH. The gene transcript was mapped for L. casei and Escherichia coli hosts. The promoter, terminator and Shine-Dalgarno sequence are functional in both organisms. The gene encodes a protein subunit of 38 kDa, whereby 67% of the sequence could be checked by correlation with partial peptide sequences from the original enzyme. So far no Lactobacillus gene has been found to utilize the Arg codons AGG and AGA.

Alcohol Oxidoreductases↗
PubMed1989

A preliminary pharmacokinetic study of 111In-labeled 260F9 anti-(breast cancer) antibody in patients.

The pharmacokinetics of 111In-labeled 260F9, a murine monoclonal antibody directed against a breast-cancer-associated antigen, was determined in seven patients with advanced breast cancer. Six patients were administered 1 mg antibody containing 1 mCi 111In. The seventh patient was administered 20 mg unlabeled antibody followed by 1 mg 111In-labeled antibody all via a peripheral vein. Immunoprecipitation, HPLC and SDS-PAGE gels demonstrated the stability of radiolabel on the antibody. The serum clearance of the radiolabel closely fits (r2 greater than 0.95) a two-compartment model for the first six patients. The apparent volume of distribution of the radiolabel approximated to the plasma volume (31) and its mean residence time was 23.7 h. The radiolabel had an average t 1/2 beta of 22.9 +/- 12.21 h at the 1-mg dose. At the 20-mg dose one-compartment elimination kinetics were observed with the radiolabel and antibody showing similar mean residence times (36-41 h) and a t 1/2 beta of 26-28 h. Whole-body imaging showed that the blood-pool: liver ratio of radioactivity increased fourfold (at 48 h postinfusion) at the higher dose and the percentage of the injected dose of radioactivity in the liver decreased from 25% to 8% (24 h postinfusion). In one patient 7-14 times more radioactivity was localized in a breast tumor than in fat (normal breast). Over the first 25 h an average (cumulative) 7.5% of the total dose was excreted in urine. A study of 260F9 in CDF-1 mice demonstrated that the radiolabel remained associated with the antibody in serum. The antibody, however, cleared 60-fold slower in mice than in patients and showed an increased mean residence time of 191 h. The disparity in the pharmacokinetics of the antibody seen in the mouse and in the clinic, points to the different behavior shown by murine monoclonal antibodies in humans. This points to the need for preliminary studies of antibodies in patients for preclinical evaluations of their effectiveness as drug-targeting agents.

Adult↗
PubMed1989

Preliminary report on isolation of mycobacteria from patients with Crohn's disease.

Several investigators have recently described the isolation of slow growing mycobacteria from the tissues of patients with Crohn's disease (CD). The primary purpose of this study was to culture and identify mycobacteria from the intestines of patients with CD and other intestinal diseases (control tissues). The culture methods were designed to eliminate most rapid-growing mycobacteria and to enhance the isolation of slow growing mycobacteria. Eighty-two surgically resected intestinal tissue samples were cultured over a four-year period: 27 tissues were from CD patients and 55 from patients with other intestinal diseases. After 4-12 months of culture, five mycobacteria were isolated, but only two have been identified thus far. Both of these organisms appeared to have initially grown as spheroplasts, but revertant bacteria were cultivated after transfer into fresh media. Four of the mycobacteria were from CD tissues, and one isolate was from a control tissue. Two of the isolates have been identified as M. chelonei subsp. abscessus, strain 390 and M. paratuberculosis strain 410. This M. paratuberculosis is similar to the previously identified M. paratuberculosis strains isolated from other human intestinal tissues from patients with CD. Both strains 390 and 410 were inoculated into neonatal goats, but they failed to reproduce a CD-like disease. The isolation of four mycobacteria from 27 CD tissues and only one from 55 control tissues strengthens the findings of previous investigators and supports the hypothesis that mycobacteria may be etiologically associated with some cases of Crohn's disease.

Animals↗
PubMed1989

The Tc3 family of transposable genetic elements in Caenorhabditis elegans.

We describe genetic and molecular properties of Tc3, a family of transposable elements in Caenorhabditis elegans. About 15 Tc3 elements are present in the genomes of several different wild-type varieties of C. elegans, but Tc3 transposition and excision are not detected in these strains. Tc3 transposition and excision occur at high frequencies, however, in strain TR679, a mutant identified because of its highly active Tc1 elements. In TR679, Tc3 is responsible for several spontaneous mutations affecting the unc-22 gene. Tc3-induced mutations are unstable, and revertants result from precise or nearly precise excision of Tc3. Although Tc3 is very active in TR679, it is not detectably active in several other mutator mutants, all of which exhibit high levels of Tc1 activity. Tc3 is 2.5 kilobases long, and except for sequences near its inverted repeat termini, it is unrelated to Tc1. The termini of Tc3 are inverted repeats of at least 70 base pairs; the terminal 8 nucleotides of Tc3 are identical to 8 of the terminal 9 nucleotides of Tc1.

Animals↗
PubMed1989

Insulin-dependent diabetes mellitus associated with pentamidine.

Insulin-dependent diabetes mellitus occurred following intravenous pentamidine treatment of two AIDS patients with Pneumocystis carinii pneumonia. Both patients also experienced drug-induced nephrotoxicity. Patients receiving pentamidine must be observed for multisystem dysfunction, including the onset of severe diabetes mellitus. Dosage adjustment or alternative therapy should be considered with the onset of toxicity.

Adult↗
PubMed1989

Correlation of prostate-specific antigen and technetium-99m HMDP bone imaging.

For an evaluation of the clinical utility of prostate-specific antigen (PSA), 32 prostatic carcinoma patients (ages 54-76) and 13 nonprostatic carcinoma patients (ages 60-70) underwent PSA measurements and bone imaging. At the time of bone imaging, each patient's PSA value was measured by a monoclonal immunoradiometric assay. All 13 nonprostatic carcinoma patients (11 bronchogenic, 1 colon, and 1 urinary bladder) gave normal PSA values, although 6 had metastatic bone disease. The 32 prostatic cancer patients were divided into 2 groups of 16 each; PSA levels in Group 1 were abnormal (greater than or equal to ng/ml): PSA levels in Group 2 were normal (less than 4 ng/ml). In Group 1, bone images of 14 patients showed bone metastases; 6 of the 14 showed progression of metastases in a 6- to 12-month period. Two patients in Group 1 were negative for skeletal metastases. Twelve patients in Group 2 were negative for skeletal metastases; bone imaging in 1 showed regression of skeletal metastases; and 3 patients had unchanged bone lesion(s). The data indicate that PSA measurements may enhance bone imaging interpretation and provide valuable clinical monitoring of prostatic carcinoma. In the case of a patient with positive bone imaging and an unknown primary, PSA measurements may definitively determine if metastases originated from prostatic carcinoma.

Aged↗
PubMed1989

Assessment of nutritional status in noninstitutionalized elderly.

Aging may modify both the availability of and needs for certain nutrients. Our study was done to assess the contribution of age alone to micronutrient levels in older volunteers (aged 60 or more). One hundred two healthy elderly white subjects, 63 women and 39 men, carefully screened by history or chart review, were studied in the fasting state. All were noninstitutionalized without serious chronic or acute illness; their diets were nutritionally adequate, containing more than two thirds of the recommended dietary allowance (RDA) for all nutrients, and no subject was taking more than twice the RDA of fat-soluble vitamins. These subjects had higher levels of plasma and red blood cell carnitine, and vitamins A, E, and C. They had lower levels of albumin, transferrin, and zinc than younger laboratory reference subjects. Retinol-binding protein, serum and red blood cell folate, and copper levels were not different. With increasing age, levels of transferrin and vitamins C and E fell; all other measured micronutrient levels were similar. Albumin, vitamin C, and copper values were higher among elderly women, and plasma and red blood cell carnitine values and zinc levels were higher in elderly men. There was great variability in the micronutrient levels despite similar nutrient intakes.

Age Factors↗
PubMed1989

Outpatient methadone programme for pregnant heroin using women.

A prospective study of pregnant narcotic users who attended the antenatal clinic at Westmead Hospital was undertaken to determine the practicality and safety of an outpatient methadone programme for these women. Forty-six women were commenced and managed on a methadone maintenance programme based at the Drug and Alcohol Clinic at Westmead Hospital (GROUP I), 12 women were maintained on long-term methadone therapy by outside prescribers (GROUP II), 12 women not on methadone continued to use heroin through the pregnancy (GROUP III), 14 women used heroin intermittently (GROUP IV). These were compared with a group of 52 women who were non-drug using (GROUP V). Women on the hospital based methadone programme had an earlier first antenatal clinic visit (p less than 0.001) than those women on outside methadone programmes or on heroin and had a longer pregnancy (p less than 0.001) than those women on heroin. The birth-weights on babies delivered to women on the Westmead Methadone Programme were significantly higher than those on babies born to women using heroin (p less than 0.05). A disappointing aspect of the study was a lower number of antenatal clinic visits (p less than 0.001) for all narcotic using women when compared with the comparison group. The outcome of the Westmead Methadone Programme women showed that better maternal and neonatal outcome followed entry into a hospital monitored methadone programme with attendant antenatal care.

Adult↗
PubMed1989

Possible function of matrix proteins in fluoride incorporation into enamel mineral during porcine amelogenesis.

The present study was undertaken to elucidate the mechanism of fluoride incorporation into secretory enamel mineral, with porcine enamel used as a model. Although the fluoride content in the enamel varied greatly among the animals, we observed that the fluoride-to-calcium ratio in the enamel tissue was maximal at the beginning of the secretory stage; the F/Ca ratio decreased (and leveled off) with the advancement of mineralization. In vitro work showed that some of the fluoride in the secretory enamel tissue was removed with the extraction of organic matter, mostly amelogenins. Furthermore, coating hydroxyapatite crystals with enamel matrix proteins resulted in a retardation of fluoride incorporation into the crystals when exposed to fluoride solutions, as a result of an inhibition of apatite reprecipitation. We also confirmed that the growth kinetics of fluoridated apatite onto HA seeds decreased with increasing coverage of the seed surface with the enamel proteins. All the results of the present study strongly suggest that the fluoride incorporation into enamel mineral during the secretory stage may be regulated by the kinetics of mineralization, which is highly dependent on the driving force for precipitation and the presence of proteinaceous inhibitors, mainly amelogenins.

Amelogenesis↗
PubMed1989

Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy.

In this phase II trial, 105 eligible patients with no prior chemotherapy and advanced sarcoma received doxorubicin, ifosfamide, and dacarbazine (DTIC) with mesna uroprotection (MAID). Starting doses of these drugs were 60, 7,500, and 900 mg/m2 divided over 72 hours by continuous infusion, respectively. Mesna was given for 84 to 96 hours at 2,500 mg/m2/d. Myelosuppression was dose limiting, causing the only toxic death (sepsis). Nonhematologic toxicity consisted predominantly of anorexia and vomiting. Severe mucositis, macroscopic hematuria, renal tubular acidosis, renal failure, and CNS toxicity occurred in less than 5% of cycles. No cardiotoxicity was detected. The overall response rate (10% complete response [CR]) was 47% (95% confidence intervals, 5% to 18% and 37% to 57%, respectively). Most responses (approximately 70%) were observed within two cycles. Median times to progression were 10 and 9 months, respectively. Histologic high tumor grade, lesions less than 5 cm, and less than 1 year from diagnosis to study entry correlated with the probability of response. The median survival was 16 months. Time from diagnosis to study entry, performance status, and extent of disease, but not histologic grade, correlated with survival. Following CR, two patients remain disease-free at 32 and 16 months. Of the 15 additional patients rendered disease-free with surgery, two remain disease-free at 30 and 18 months with no further therapy. While most relapses occurred in sites of prior involvement, death from CNS metastases occurred in 11 of the 80 patients with high-grade sarcomas, of whom seven were still responding systematically (three complete responders). Because of its substantial response in this phase II trial, the MAID regimen is being compared with doxorubicin and DTIC alone in advanced sarcomas and to observation in the adjuvant treatment of high-grade sarcomas in randomized trials.

Actuarial Analysis↗