Search PubMed⌕ Search

Biomedical subjects

A R Miller

Publications and source records attributed to A R Miller.

At least 19 recordsLinked to original sources
PubMed1999

In vivo adenoviral delivery of recombinant human protein kinase C-zeta stimulates glucose transport activity in rat skeletal muscle.

An in vivo adenoviral gene delivery system was utilized to assess the effect of overexpressing protein kinase C (PKC)-zeta on rat skeletal muscle glucose transport activity. Female lean Zucker rats were injected with adenoviral/human PKC-zeta (hPKC-zeta) and adenoviral/LacZ in opposing tibialis anterior muscles. One week subsequent to adenoviral/gene delivery rats were subjected to hind limb perfusion. The hPKC-zeta protein was expressed at the same level (fast-twitch white) or at approximately 80% of the level (fast-twitch red) of endogenous PKC-zeta, thus approximately doubling the amount of PKC-zeta in tibialis anterior. Basal glucose transport activity was elevated approximately 3.4- and 2-fold, respectively, in fast-twitch white and red hPKC-zeta muscle relative to control. Submaximal insulin-stimulated glucose transport activity, corrected for basal transport, was approximately 90 and 40% over control values, respectively, in fast-twitch white and red hPKC-zeta muscle. The enhancement of glucose transport activity in muscle expressing hPKC-zeta occurred in the absence of any change in GLUT1 or GLUT4 protein levels, suggesting a redistribution of existing transporters to the cell surface. These results demonstrate that an adenoviral vector can be used to deliver expressible hPKC-zeta to adult rat skeletal muscle in vivo and also affirm a role for PKC-zeta in the regulation of glucose transport activity.

Adenoviridae↗
PubMed1999

The incidence and clinical consequences of treatment-related bowel injury.

OBJECTIVE: To assess the frequency and clinical features of treatment-induced bowel injury in rectal carcinoma patients receiving perioperative external beam radiotherapy (EBRT). The frequency of and factors associated with treatment-induced intestinal injury have previously not been well quantified for rectal cancer patients. Postoperative adjuvant chemoirradiation is recommended for Stage II and III rectal cancers, making such data of significant interest. METHODS AND MATERIALS: The records of 386 consecutive patients undergoing radiotherapy with or without chemotherapy (CT) for rectal carcinoma between 1981-90 were reviewed. Eight-two patients were excluded for receiving nontherapeutic EBRT or modalities other than EBRT. RESULTS: Symptomatic acute treatment-related enteritis (within 30 days of EBRT +/- CT) was diagnosed in 13 patients, 3 of whom developed chronic bowel injury. Chronic treatment-related enteritis was identified in 18 patients and reoperation was required in 17 (5% of the 304 patients with complete follow-up). Chronic proctitis was documented in 38 patients, including 3 patients with small bowel injury. The probability of developing treatment-induced bowel injury at 5 years following treatment was 19%. Variables associated with an increased risk of bowel injury using multivariate analysis were transanal excision (p = 0.002), escalating radiation dose (p = 0.005), and increasing age (p = 0.01). Twenty of the affected patients required operative treatment, and 2 deaths resulted from treatment-induced enteritis. CONCLUSION: Patients with rectal carcinoma treated with EBRT +/- CT have the risk of developing treatment-induced bowel injury. The pelvic radiation dose should be limited to < or = 5040 cGy unless small bowel can be displaced. Reperitonealization of the pelvis, or other surgical methods of excluding the small intestine should be used whenever possible.

Aged↗
PubMed1999

Psychiatric symptoms endorsed by somatization disorder patients in a psychiatric clinic.

Patients with somatization disorder (SD) endorse high rates of psychiatric symptoms. However, prior studies have not addressed whether these endorsed symptoms reflect underlying psychiatric illness or whether they represent symptom overendorsement mirroring somatic complaints in patients with SD. Thirty-two female outpatients with SD and 101 with other psychiatric disorders completed a checklist of current and lifetime psychiatric symptoms. These findings were analyzed with respect to the diagnoses given by their treating psychiatrists. Patients with SD displayed significantly more current and lifetime psychiatric symptoms than did patients without either SD or cluster B personality disorder. Patients with SD endorsed a large number of psychotic, manic, depressive, and anxiety symptoms; however, they endorsed few alcohol use disorder symptoms. Psychotic and manic symptoms endorsed by patients with SD did not reflect their clinical diagnoses: only two patients with SD carried an additional clinician diagnosis of either schizophrenia or bipolar disorder, despite high rates of endorsed symptoms by the group. Patients with cluster B personality disorders but without SD showed a symptom profile similar to that of patients with SD. Psychiatric outpatients with SD endorse many more psychiatric symptoms than do other psychiatric patients. Patients with SD in the psychiatric treatment setting may mimic other psychiatric illnesses; therefore, SD should be considered in the differential diagnosis for a wide variety of psychiatric illness, including psychotic and mood disorders.

Adolescent↗
PubMed1999

Removal of low concentrations of carbon tetrachloride in compost-based biofilters operated under methanogenic conditions.

Research was performed to demonstrate the removal of carbon tetrachloride (CT) using compost biofilters operated under methanogenic conditions. Biofilters were operated at an empty-bed residence time of 2.8 minutes using nitrogen as the atmosphere. Hydrogen and carbon dioxide were supplied as an electron donor and carbon source, respectively, during acclimation of the bed medium microbes. Once methanogenesis was demonstrated, CT flow to the biofilter was established. Biofilters were operated over a CT concentration range from 20 to 700 ppbv for 6 months. Bed medium microbes were able to remove up to 75% of the inlet CT. At excessively high CT concentrations (> 500 ppmv), methane production and hydrogen utilization by the bed medium microbes appeared to be inhibited. CT removal by the biofilter decreased when the hydrogen supply was removed from the biofilter inlet, indicating that hydrogen acted as the electron donor for reductive dechlorination. The removal efficiency and relatively low empty bed residence times demonstrated by these laboratory-scale biofilters indicate that anaerobic biofiltration of CT may be a feasible full-scale process.

Carbon Tetrachloride↗
PubMed1999

Effects of long daily photoperiod and bovine somatotropin (Trobest) on milk yield in cows.

Bovine somatotropin (bST) and exposure to long daily photoperiod increase milk yield of dairy cattle. We tested the hypothesis that long daily photoperiod and bST treatment would increase milk yield in an additive manner in lactating cows. At winter solstice, 40 lactating cows were started on a 140-d experiment; cows were greater than 70 d in milk (DIM) and were balanced for uniformity of DIM and milk yield within parity. Cows were randomly assigned to one of four treatments (10/treatment): 1) natural photoperiod, 2) natural photoperiod + bST (14 mg/d Trobest i.m.), 3) long daily photoperiod (18 h of light and 6 h of darkness/d), or 4) long daily photoperiod + bST. Long daily photoperiod increased fat-corrected milk (FCM) yield 1.9 kg/d versus natural photoperiod. Treatment with bST increased FCM 5.7 kg/d versus natural photoperiod, and long daily photoperiod + bST increased FCM 5.8 kg/d versus long daily photoperiod. Long daily photoperiod + bST was additive, increasing FCM 7.7 kg/d versus natural photoperiod. Serum somatotropin increased with bST, but not photoperiod, and bST increased serum insulin-like growth factor-I. Long daily photoperiod tended to increase prolactin; bST had no effect. Long daily photoperiod + bST increased dry matter intake (DMI) relative to natural photoperiod and natural photoperiod + bST; long daily photoperiod increased DMI relative to natural photoperiod + bST. Photoperiod had no effect on net energy balance; however, bST decreased net energy balance. Generally, body weight and milk composition did not differ among treatments. In conclusion, combination of bST with long-daily photoperiod tended to amplify the increases in milk yield observed with either treatment individually.

Animals↗
PubMed1998

Dynamics of carriage of Neisseria meningitidis in a group of military recruits: subtype stability and specificity of the immune response following colonization.

Meningococcal carriage and the immune response to colonization were studied in a group of military recruits undergoing basic training. Subtyping by determination of the class 1 protein sequence clearly differentiated between strains and demonstrated the dynamics of carriage and transmission. Expression of class 1 protein by each strain remained stable during prolonged carriage by different subjects. Following colonization, a marked increase in serum bactericidal response occurred, which was specific for the subtype of the acquired strain and was associated with an increase in reactivity by Western blot to the homologous class 1 protein. Subjects colonized by multiple strains showed evidence of a specific immune response to the class 1 protein of each strain acquired. The subtype specificity of the bactericidal response to meningococci and the stability of expression of the class 1 protein have important implications for the design of vaccines for prevention of serogroup B meningococcal disease.

Antibodies, Bacterial↗
PubMed1998

HIV enteropathy: comparative morphometry of the jejunal mucosa of HIV infected patients resident in the United Kingdom and Uganda.

AIMS: To compare jejunal mucosal morphometry in HIV infected patients resident in London and Uganda. PATIENTS: Twenty HIV positive patients from London and 16 from Uganda were studied, and compared with HIV negative control subjects from both sites. METHODS: Stools and biopsy specimens were examined for enteropathogens. Surface area to volume (S:V) ratio was estimated morphometrically, mean crypt length of jejunal biopsy specimens was measured, and HIV infected cells detected immunohistochemically were quantified. RESULTS: Enteric pathogens were detected in none of the London patients, and in three Ugandan patients. S:V ratio was lower, and mean crypt length higher, in the specimens of London patients than in normal subjects, but there was no difference in S:V ratio or mean crypt length between Ugandan patients and controls. A negative correlation was present between S:V ratio and mean crypt length in all biopsy specimens analysed. HIV infected cells were detected only in lamina propria. CONCLUSION: Infection of cells in the lamina propria of the jejunum with HIV stimulates crypt cell proliferation, and a fall in villous surface area. The mucosal response to HIV is masked by other pathogens in the African environment.

Adult↗
PubMed1998

Neoadjuvant chemoradiation for adenocarcinoma of the pancreas.

Pancreaticoduodenectomy is performed on carefully selected patients as part of a protocol-based clinical research program emphasizing the importance of multimodality management for patients with potentially resectable adenocarcinoma of the pancreatic head. Treatment schemas emphasize the importance of minimizing toxicity and treatment duration, while attempting to improve therapeutic efficacy. Cytotoxicity is enhanced by combining radiation therapy with more potent radiation-sensitizing agents. Because of the high incidence of liver metastases, systemic therapy is continued after chemoradiation and surgery with systemic agents of low toxicity directed at specific molecular events involved in pancreatic tumorigenesis such as inhibition of angiogenesis, induction of apoptosis, or arrest of the cell cycle.

Adenocarcinoma↗
PubMed1998

Reversible ischemic neurologic deficit after ECT.

We report the case of a 58-year-old woman with depression and hypertension in whom aphasia, right-sided hemiparesis, and a possible right visual field defect were identified during recovery from right unilateral electroconvulsive therapy (ECT). The neurologic deficits resolved over a 3-day period; the patient was diagnosed with a reversible ischemic neurologic deficit (RIND). Review of the patient literature suggests that such cerebrovascular events in the setting of ECT are extremely rare and possibly decreasing in frequency. Reasons for such a decrease may include improved screening for predisposing cardiovascular conditions and the widespread use of neuromuscular blockade, ventilatory support, and cardiovascular monitoring during the procedure. Prompt recognition of cerebrovascular events is important to prevent complications such as cerebral edema, seizures, and aspiration, as well as to use new treatments for stroke.

Ancrod↗
PubMed1997

"Profile" analysis of the personality characteristics of child molesters using the MMPI-2.

Identification of child sexual molesters has been attempted for at least half a century without success. This is due, in part, to the heterogeneity of child molesters. Child sexual molesters were studied in three ways. First, a discriminant function analysis was conducted to evaluate how well the MMPI-2 would distinguish child molesters from controls. Hit rates of 81% and 88% were found for clinical scales alone and the clinical and supplemental scales, respectively. Second, a cluster analysis of MMPI-2 data identified four groups that resembled clusters found previously with the MMPI. Third, when followed in treatment, all subgroups achieved significant progress ratings and no significant difference in treatment progress was found between clusters.

Adolescent↗
PubMed1997

Transduction of murine and human tumors using recombinant adenovirus vectors.

BACKGROUND: Most cytokine-based cancer gene therapy clinical trials have used labor-intensive, retrovirus-mediated strategies resulting in unpredictable gene expression. Recombinant AdV vectors were evaluated for easier, more reproducible gene transfer into 12 human melanoma, 2 murine fibrosarcomas, and 8 other tumor cell lines. METHODS: AdV vectors contained a reporter (Escherichia coli beta-galactosidase or firefly luciferase) or cytokine gene (human interleukin-2 [IL-2] or IL-7). Transduction efficiencies and expression levels were assessed by histochemical staining, flow cytometry, polymerase chain reaction, fluorometry, and enzyme-linked immunosorbent assay. Tumorigenicity was determined by subcutaneous injection of cells into syngeneic mice. RESULTS: All cell lines studied were transduced with AdV. Most cell lines exhibited 100% transduction efficiencies (by flow cytometry) at multiplicities of infection (MOI) epsilon 10. Gene expression correlated linearly with MOI, but a cytopathic effect was observed at MOI > 100 with all vectors. Nanogram gene expression levels were routinely achieved. Irradiation (30 Gy) minimally affected expression levels. Tumorigenicity of AdV-IL-2-transduced fibrosarcoma cells in mice was inversely related to IL-2 production. A majority of mice that rejected their tumor challenge were immune to tumor rechallenge. CONCLUSIONS: E1-deleted AdV vectors may prove useful in generating tumor vaccines ex vivo with high, transient cytokine expression levels.

Adenoviridae↗
PubMed1997

Multifunctional cytokine expression by human mast cells: regulation by T cell membrane contact and glucocorticoids.

Human mast cells readily release a variety of mediators, including cytokines, in response to IgE receptor crosslinking, but the mechanisms governing the expression of cytokines are still unclear. Using a human mast cell line, HMC-1, we show expression of cytokine transcripts as early as 2 h after activation with ionomycin and phorbol myristate acetate (PMA). Resting HMC-1 cells expressed transcripts for interleukin-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-5, GM-CSF, and weakly for IL-8, and stimulation with ionomycin and PMA induced additional transcripts for IL-6 and IL-13 and upregulated expression of IL-8 transcripts. HMC-1 cells secreted IL-4, IL-8, and GM-CSF protein after activation and dexamethasone significantly inhibited the production of these cytokines. Of significance is the finding that the addition of membranes purified from activated T cells to mast cell cultures induced transcripts selectively for IL-8 and none for other proinflammatory cytokines. Flow cytometry revealed that resting HMC-1 cells express CD40, a molecule involved in contact-dependent signaling of monocytes and B cells by T cells. However, activation of HMC-1 by anti-CD40 antibody did not induce IL-8 gene expression or protein production. This study demonstrates that human mast cells are capable of expressing multiple cytokines that can be inhibited by glucocorticoids. It also raises the possibility that T cells may activate mast cell cytokine synthesis by novel contact-dependent mechanisms. This phenomenon of T cell regulation of mast cell function requires further study.

Anti-Inflammatory Agents↗
PubMed1997

A new technique for removal of intraarticular bullet fragments from the femoral head.

Removal of foreign bodies from a joint usually involves an extensive surgical approach. The necessity for intraarticular bullet removal has been well documented in the literature. The conventional approach for bullet extraction usually requires an open arthrotomy, arthroscopic removal or, in most cases, a combination of the two. This report involves a previously undocumented technique for bullet removal from the hip. A Synthes DHS Triple Reamer was inserted through a limited lateral incision over a guide pin that had been placed under fluoroscopic guidance. The tip of the guide pin was positioned in contact against the bullet fragments in both the anteroposterior and lateral planes. The fragments were then removed through the reamed canal. This technique allows for bullet removal without the inherent risks associated with an open arthrotomy and without the special skills required for hip arthroscopy. It is relatively easy to perform and may prove to be a valuable tool in the arsenal of orthopedists who deal with specific gunshot wounds to the hip region.

Adult↗
PubMed1996

Cytokine priming reduces dependence on TNF-R2 for TNF-alpha-mediated induction of macrophage nitric oxide generation.

In the presence of interferon-gamma (IFN-gamma), human tumor necrosis factor-alpha (Hu-TNF-alpha), which binds to murine TNF-alpha receptor type 1 (TNF-R1) but not to murine TNF-R2, was effective in inducing nitric oxide (NO) production in spleen-derived macrophages (M phi), albeit at concentrations 12.5-fold greater than those required by murine TNF-alpha (Mu-TNF-alpha), to achieve the same result. Addition of anti-TNF-R1 completely inhibited the Mu-TNF-alpha-mediated induction of NO, demonstrating that TNF-R1 is critical to the IFN-gamma-dependent TNF-alpha-mediated induction of M phi effector function. However, treatment with anti-TNF-R2 resulted in a partial inhibition of M phi activation. Spleen-derived M phi were more dependent on TNF-R2 than RAW 264.7 or peritoneal M phi based on their responsiveness to Hu-TNF-alpha. Priming of spleen-derived M phi with either IFN-gamma or granulocyte-macrophage colony-stimulating factor (GM-CSF) heightened the maximal responses to both TNF-alpha species and increased the overall effectiveness of Hu-TNF-alpha without increasing expression of either TNF-alpha receptor. The dependence of spleen-derived M phi on both TNF-alpha receptors for signaling the induction of effector function supports an active signaling role for TNF-R2 in its synergy with TNF-R1 rather than a passive ligand passing role.

Animals↗