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Biomedical subjects

J Hoffman

Publications and source records attributed to J Hoffman.

At least 145 records · Page 8Linked to original sources

Diagnostic epidural opioid technique.

Diagnostic epidural blocks were performed on 27 chronic pain patients sequentially using saline, fentanyl, and lidocaine solution. The patients were divided into one of four groups based on their response to the epidural solutions: placebo response group--pain relief with placebo solutions; fentanyl response group--pain relief with epidural fentanyl; lidocaine response group (LRG)--pain relief with lidocaine but not fentanyl; and no response group--no pain relief with any of the solutions used. The four groups were compared on the basis of age, sex, site of pain, duration of pain, narcotic use, pain assessment index, and workmen's compensation claims. The comparisons resulted in the conclusion that LRG patients had a much longer average duration of pain than the other groups. On the basis of the information gathered, it was theorized that, despite their response to epidural lidocaine, LRG patients may actually be a group of operant pain patients. Their failure to receive analgesia from epidural fentanyl may be a learned response such that they associate any sensory input from the affected area as painful. If follow-up studies support these findings, then the diagnostic opioid technique may be a more sensitive tool in diagnosing chronic pain.

Adult↗

Stimulation of the human immunodeficiency virus type 1 enhancer by the human T-cell leukemia virus type I tax gene product involves the action of inducible cellular proteins.

The human immunodeficiency virus type 1 (HIV-1) preferentially infects CD4+ T lymphocytes and may exist as a latent provirus within these cells for extended periods. The transition to a productive retroviral infection results in T-cell death and clinically may lead to the acquired immune deficiency syndrome. Accelerated production of infectious HIV-1 virions appears to be closely linked to a heightened state of T-cell activation. The transactivator (Tax) protein of the type I human T-cell leukemia virus (HTLV-I) can produce such an activated T-cell phenotype and augments activity of the HIV-1 long terminal repeat. One Tax-responsive region within the HIV-1 long terminal repeat has been mapped to a locus composed of two 10-base-pair direct repeats sharing homology with the binding site for the eucaryotic transcription factor NF-kappaB (GGGACTTTCC). Tax-expressing Jurkat T cells contain one or more inducible cellular proteins that specifically associate with the HIV-1 enhancer at these binding sites. Microscale DNA affinity precipitation assays identified a Tax-inducible 86-kilodalton protein, HIVEN86A, as one of these HIV-1 enhancer-binding factors. The interaction of HIVEN86A, and presumably other cellular proteins, with the HIV-1 enhancer appears functionally important as oligonucleotides corresponding to this enhancer were sufficient to impart Tax inducibility to an unresponsive heterologous promoter. These findings suggest that the Tax-inducible cellular protein HIVEN86A plays an important role in the transcriptional activation of the HIV-1 enhancer. These specific protein-DNA interactions may also be important for the transition of HIV-1 from a latent to a productive mode of infection. Furthermore, these findings highlight an intriguing biological interplay between HTLV-1 and HIV-1 through a cellular transcriptional pathway that is normally involved in T-cell activation and growth.

Cell Line↗

A nonsense mutation in the apolipoprotein C-IIPadova gene in a patient with apolipoprotein C-II deficiency.

The apo C-II gene from a patient with apo C-II deficiency has been sequenced after amplification by the polymerase chain reaction. A substitution of an adenosine for a guanosine at position 3002 in exon 3 of the patient's gene was identified by sequence analysis. This mutation leads to the introduction of a premature termination codon (TAA) at a position corresponding to amino acid 37 of mature apo C-II and to the formation of a new Rsa I restriction enzyme site not present in the normal apo C-II gene. Amplification of DNA from family members by the polymerase chain reaction and digestion with Rsa I established that the patient is a true homozygote for the mutation. Analysis of the patient's plasma by two-dimensional gel electrophoresis and immunoblotting detected an apo C-II that exhibited abnormal electrophoretic mobility. We propose that the C to A substitution in the apo C-IIPadova gene is the primary genetic defect that leads to premature termination and the synthesis of a truncated 36 amino acid apo C-II that is unable to activate lipoprotein lipase.

Adenosine↗

The angiocardiographic diagnosis of a persistent truncus arteriosus in a foal.

Persistent truncus arteriosus is a relatively rare cardiac anomaly which is associated with a single large artery arising from the ventricles. An interventricular septal defect is invariably present. The vessel gives origin to the pulmonary trunk, aorta and coronary arteries. A description of the angiocardiographic diagnosis of this condition is given as well as a general review of the relative developmental anatomy.

Angiocardiography↗

Determination of interchain crosslinkages in insulin B-chain dimers by fast atom bombardment mass spectrometry.

New methodology for identifying and locating crosslinkages in peptides is described. Pepsin is used to cleave insulin and B-chain dimers of insulin into fragments under conditions which retain the original peptide crosslinkages. After partial separation by HPLC, the peptides are analyzed by fast atom bombardment mass spectrometry (FABMS) to determine their molecular weights. The molecular weights of peptide fragments expected from the pepsin digests of human insulin and related model compounds are calculated from the amino acid sequence of the intact peptide. Digestion products are identified by matching their molecular weights, as determined by FABMS, with calculated molecular weights. Locations of interchain crosslinkages are deduced after the peptide fragments have been assigned to specific segments of the parent peptide. The validity of the method has been established by correctly identifying structurally important products in the pepsin digests of model compounds such as human, bovine, and porcine insulins. Procedures developed with the model compounds were used to identify crosslinkages in peptides of unknown structure isolated from an insulin A-chain/B-chain combination reaction mixture. Evidence is presented for formation of three different types of crosslinkages, disulfide, lanthionine, and sulfoxide.

Amino Acid Sequence↗

Imaging pattern of previously in vitro sensitized and interleukin-2 expanded autologous lymphocytes in human cancer.

In vivo patterns of lymphocytes sensitized against autologous tumor (in vitro) were studied in seven patients with metastatic cancer as a potential candidate for an alternative method of radioimmunodetection and adoptive immunocytotherapy. Peripheral blood lymphocytes (PBL) were either activated in Interleukin-2 (IL-2) [lymphokine activated killer (LAK) cells] or sensitized against autologous tumor cells by in vitro co-culture (IVC) and expanded in IL-2 (educated cells); both were then labelled with 111In. Labelled autologous cells (1 x 10(7)-5 x 10(8)) were administered to patients and biodistribution studied by imaging under a gamma camera at various time intervals. In 4/7 cases, imaging with the educated cells showed concentrations of radioactivity at sites that correlated positively with clinically detectable metastatic tumor. By contrast, only one instance of positive uptake was seen with the LAK cells. Other than slight fever in three cases, infusions of labelled PBL were well tolerated. Educated lymphocytes were cytotoxic against autologous tumor cells and the cytotoxic reactivities of the educated cells were maintained in continuous culture in IL-2 for 4-6 weeks. Evidence of accumulation of radiolabelled educated autologous cells at a significantly higher frequency than that of the LAK cells suggests that in vitro expanded educated PBL might be better candidates for radioimmunodetection of human cancer, and continuous cultures of such educated autologous PBL might be sources for repeated administration of these effector cells.

Adult↗

Candida epiglottitis in an adult with acute nonlymphocytic leukemia.

A 40-year-old white woman presented with fever, otalgia, and odynophagia and was found to have a peripheral white blood cell count of 90,000/mm3. A diagnosis of acute myelogenous leukemia was made. Further evaluation of symptoms and source for fever led to the diagnosis of Candida albicans epiglottitis. This is the first reported case of fungal epiglottitis in an immunocompromised adult.

Adult↗

Activation of human serum complement by bacterial lipopolysaccharides: structural requirements for antibody independent activation of the classical and alternative pathways.

A variety of bacterial lipopolysaccharide (LPS) preparations with highly defined primary polysaccharide chemical structure and/or aggregate macromolecular composition have been employed to examine the molecular requirements for activation of the classical and alternative pathways of human serum complement. Evidence is presented for two independent modes of polysaccharide dependent activation of the APC by LPS. One mechanism is dependent upon specific O-antigen polysaccharides and the second is defined by a specific L-glycero-D-mannoheptose/glucose region of the core oligosaccharide. LPS O-antigen polysaccharide but not core oligosaccharide determinants can convert sheep erythrocytes to cells capable of initiating the APC. The data presented provide convincing evidence that the tertiary assembly of individual LPS subunits into an aggregate macromolecule is a critical determinant in the expression of APC activity by LPS. The results of these studies provide strong evidence that CPC activation by LPS is restricted to the Re-chemotype and isolated lipid A. LPS isolated from other R-chemotypes as well as native wild type LPS preparations do not activate the CPC, in spite of the fact that the former LPS preparations contain more lipid A than polysaccharide on a percentage by wt basis. The presence of core polysaccharide L-glycero-D-mannoheptose, which provides a critical recognition role for activation of the APC, appears to negatively regulate CPC activation in a similar inverse relationship. In addition, the presence of polysaccharide containing LPS subunits in synthetic mixed LPS micellar aggregates can also restrict CPC activation by Re LPS subunits, most probably by steric hindrance at the LPS macromolecular surface. Our data are consistent with the hypothesis that activation of either pathway of human serum complement by a given LPS preparation is a mutually exclusive event dictated by the presence or absence of L-glycero-D-mannoheptose.

Complement Activation↗

Parenteral nutrition with associated cholelithiasis: another iatrogenic disease of infants and children.

During the past decade, 246 infants and children treated at the Columbus Children's Hospital have required more than 4 weeks of parenteral nutrition (PN). Of the 178 survivors, 70 returned for evaluation. Sixty-eight either had adequate visualization of the gallbladder by ultrasound or had previous gallbladder surgery (39%). Of 68 children who did not survive, complete postmortem examinations or ultrasound studies were available for 16 (24%). A diagnosis of cholelithiasis was established in 11 of the 84 studied patients (13%). Six of these children (55%) have required cholecystectomy for relief of chronic abdominal pain, pancreatitis, or empyema of the gallbladder. One additional infant underwent cholecystostomy. Two of the four remaining patients are asymptomatic, one has episodes of abdominal colic, and one child expired of chronic hepatic insufficiency as a result of PN-associated cholestasis. Risk factors that predisposed these children to cholelithiasis included short bowel syndrome, lack of an ileocecal valve, and an increased number of abdominal operative procedures (P less than .05). Patients with biliary calculi also had a longer duration of parenteral feeding, and a higher incidence of both PN-associated cholestasis and necrotizing enterocolitis. The intergroup differences for these characteristics, however, did not achieve statistical significance. On the basis of this information, routine ultrasound examinations of the gallbladder are recommended for children maintained on PN for longer than 30 days. All patients presenting with abdominal pain who previously received PN should also be evaluated. Early elective cholecystectomy is suggested for children who develop PN-associated cholelithiasis.

Adolescent↗

The protective effect of beta 1-3D-glucan-derivatized plastic beads against Escherichia coli infection in mice.

Pretreatment with beta-1,3-D-glucan-derivatized plastic beads conferred strong protection against Escherichia coli infection in mice. The protective effect showed a dose-response relationship to the amount of beads injected and was dependent on the time point of the injection relative to the infection with E. coli. A similar protection could be obtained in nude mice. Experiments with radioactively labelled bacteria as well as beads indicated a systemic effect of the beads. Macrophages extracted from animals treated with glucan plastic beads appeared highly stimulated. This was also true of cells that did not contain beads and presumably therefore not glucan, which seems to indicate a soluble stimulatory factor.

Animals↗

Protection by aminated glucan in experimental endogenous peritonitis.

The effect of prophylactic intraperitoneal aminated glucan on the survival rate and formation of adhesions and abscesses was investigated in rats with acute and subacute peritonitis, respectively induced by cecal perforation and ileal ligation. A significantly reduced mortality was found in both forms of peritonitis. Pretreatment by aminated glucan also significantly reduced the number of abscesses and peritoneal adhesions. An about threefold increase in peritoneal macrophages in aminated glucan-treated rats compared to controls was noted. In vitro studies, using 32P-labelled Escherichia coli, demonstrated that peritoneal macrophages from aminated glucan-treated rats had an enhanced ability to engulf and degrade bacteria. Scanning electron microscopy showed that macrophages from aminated glucan-treated animals were highly spread with prominent ruffling and bacteria located intracellularly, as opposed to macrophages from controls which were rounded with bacteria on the cell surface.

Abscess↗

Increased creatine kinase activity in pituitary tumours of rat and man.

The demonstration that phosphocreatine is used as an energy source by rat PRL-secreting pituitary tumours prompted the study of the enzyme creatine kinase in both rat and human pituitary tumours. Rats treated with diethylstilbestrol developed greatly enlarged pituitaries and hyperprolactinaemia. Total creatine kinase was significantly increased and fractionation on diethylaminoethyl Sephadex showed that the 'brain' form was increased, whereas the 'muscle' and mitochondrial forms showed no change. Exposure to large concentrations of oestradiol caused similar changes in creatine kinase which increased over a period of 25 weeks. The total creatine kinase content of a series of human pituitary tumours was highly variable, but the mean value of 183 +/- 46 (SEM) units per gram protein was significantly higher than the mean for normal pituitary tissues (28.4 +/- 2.9). The brain:muscle isozyme ratio was measured in six human PRL-secreting tumours with a mean of 3.47 +/- 0.73, significantly higher than in 'non-functional' tumours (1.57 +/- 0.29) or normal tissue (1.77 +/- 0.28). Three of four GH-secreting tumours had a ratio below 0.6. The highest ratio found (8.66) was in an ACTH-secreting tumour. Previous reports have shown that oestradiol rapidly induces brain creatine kinase in oestrogen responsive tissues. This is not the case with the rat pituitary gland or oestrogen responsive human tumour cells in culture. Chronic oestrogen treatment, however, does increase creatine kinase in the proliferating gland and many human pituitary tumours have increased enzyme activity. These results suggest that the phosphocreatine/ATP system and in particular the brain isozyme of creatine kinase are of particular importance in lactotropes.

Adenoma↗

The effect of splenectomy on Escherichia coli sepsis and its treatment with semisoluble aminated glucan.

Rats were subjected to sham laparotomy or splenectomy and were challenged with either 0.2 X 10(9) Escherichia coli intravenously or 1 X 10(9) E. coli intraperitoneally. By means of quantitative blood culturing asplenic animals were shown to have a significantly impaired ability to clear the bacteria in both forms of challenge. Treatment with intraperitoneally injected semisoluble aminated glucan (SAG), known to have strong macrophage-stimulatory properties, compensated completely for the asplenic state. The substance protected against postsplenectomy sepsis both when given before and when given after removal of the spleen. This protective effect of SAG seemed to last at least 3 weeks.

Animals↗

Treatment of experimental peritonitis in rats by transfer of peritoneal mononuclear cells from rats injected with semisoluble aminated glucan.

The efficacy of treatment with semisoluble aminated glucan (s.a.g.) and donor peritoneal mononuclear cells was investigated in two separate models of peritonitis (exogenous Escherichia coli challenge or caecal perforation). Intraperitoneal administration of s.a.g. significantly protected against both forms of peritonitis. Our previous studies indicated this protective effect to be mediated by macrophage activation, and this was corroborated by the effect of injecting rats with s.a.g.-stimulated donor peritoneal cells (approximately 95% macrophages) immediately after induction of peritonitis. Increased bacterial clearance and survival time were achieved with this treatment as compared with rats injected with cells from saline-treated donors. Scanning electron microscopy demonstrated activation of macrophages from the s.a.g.-treated rats. The results provided further support for the concept that s.a.g. exerts its therapeutic effect by stimulation of macrophages.

Animals↗