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Biomedical subjects

J Mills

Publications and source records attributed to J Mills.

At least 37 records · Page 2Linked to original sources
PubMed2001

Time-related decay of the benefits of biofeedback therapy.

Although immediate results are good to excellent in great majority of patients who undergo biofeedback treatment (BFT) for chronic constipation and fecal incontinence, they tend to loose the benefit over a period of time. The purpose of this study was to evaluate the long-term sustainability of results after successful biofeedback treatment. Two groups of patients who successfully completed BFT at our institution from 1995 to 1997 were created based on the date of completion. The first had a mean follow-up of 35 months and the second group was followed for an average of 12 months. Both groups were questioned as to the presence of constipation and incontinence. The questioning was focused depending on the patient's diagnosis. This information was then compared with the initial BFT results. Overall, all patients were satisfied by the initial BFT results. All patients initially had an excellent or good response to BFT. However, after a mean of 35 months, in the first group, 19 of 22 patients had a near complete regression back to their pre-biofeedback status. In the 14 patients in the second group with mean follow-up of 12 months, 11 had a significant decay in benefits. Only time was a significant factor in the decay of BFT benefits. In conclusion, BFT is highly effective in the treatment of selected patients with complex defecation disorders. Although there is a high initial success rate, there is a clear loss of the immediate benefits over time. Other factors such as dietary habits, pelvic floor exercises, manometry, invasive EMG, and rectal sensation did not correlate with long-term outcomes. The comparison between the two groups reveals a linear model describing the time decay of the benefits of BFT. Based on the linear model, patients may need reevaluation after one year and may benefit from additional BFT.

Adult↗
PubMed2001

The natural history of Hendra and Nipah viruses.

Pteropid bats (flying foxes), species of which are the probable natural host of both Hendra and Nipah viruses, occur in overlapping populations from India to Australia. Ecological changes associated with land use and with animal husbandry practices appear most likely to be associated with the emergence of these two agents.

Animals↗
PubMed2001

An examination of signs of disease progression in survivors of the Sydney Blood Bank Cohort (SBBC).

BACKGROUND: The Sydney Blood Bank Cohort (SBBC) was infected between 1981 and 1984 with a nef/LTR defective strain of HIV-1. Different responses to HIV-1 infection have emerged between cohort members in the last 5 years. Three recipients (C135, C64 and C49) remain asymptomatic, have normal CD4 T cell counts, below detection (BD) viral loads (VL), remain therapy naive and are termed long-term non-progressors (LTNP). The donor (D36) and the two recipients (C98 and C54) have significantly declining CD4 T cell counts, detectable VL and are now long-term survivors (LTS). In contrast, in the SA cohort, comparison study group for the SBBC, five of 24 remain therapy naïve after 15 years infection with HIV-1 and all have detectable VL. OBJECTIVES: This paper examines different outcomes to long-term infection with HIV-1 in the SBBC and provides a brief overview of the therapy naïve in a comparison study group, the SA cohort. STUDY DESIGN: Retrospective epidemiological follow-up of the SBBC and the SA cohort has been conducted for >15 years. Analysis of CD4 T cell counts, VL and intermittent monitoring of HIV-specific proliferative responses are reviewed. Viral sequence changes in the SBBC will be considered. RESULTS: Prior to therapy D36 had a CD4 T cell count of 160/mm(3) and plasma VL of 9900 copies/ml while C98 had a CD4 T cell count of 387/mm(3) and plasma VL of 11491 copies/ml. After 1 month of therapy, plasma VL was BD (<400 copies/ml) and both showed significant increase in CD4 T cell counts. Molecular changes have occurred in D36 and C98 viral strains, the most recently evolved quasispecies have larger deletions in the nef/LTR region. CONCLUSIONS: Infection with nef/LTR deleted HIV-1 has resulted in slower disease progression for the SBBC. The three LTNP have maintained normal low levels of activated CD8 T cells and strong HIV-specific proliferative responses to HIV-1 p24, which are associated with control of viral replication.

Australia↗
PubMed2001

Preventive and therapeutic strategies for respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) remains an important cause of pneumonitis in infants and in the elderly and immunosuppressed. Passive immunoprophylaxis of high-risk infants with the humanised monoclonal antibody palivizumab reduces RSV-related hospitalisation and admission to intensive care units by about 50%, although optimal and cost-effective use of this agent remains undefined. The development of an RSV vaccine is the focus of much research and recent advances with live attenuated vaccines are promising--several agents are in clinical trials. The value of the only therapeutic agent available to treat established infection, the antiviral ribavirin, is now seriously doubted and the agent is little used. New RSV chemotherapeutics are just entering clinical trials.

Animals↗
PubMed2001

Seasonal variation in prevalence of antibody to hantaviruses in rodents from southern Argentina.

We conducted a small mammal trapping study to investigate temporal variation in prevalence of infection in hantavirus reservoir populations in the Patagonian Andes mountain range, Rio Negro province, Argentina. Rodent blood samples collected in natural and periurban habitats and at the home of an hantavirus pulmonary syndrome (HPS) case patient were analysed by enzyme-linked immunosorbent assay. Organ tissue samples were tested by polymerase chain reaction (PCR) and nucleotide sequence analysis. Eight species of 1032 rodents were captured in 15 551 trap nights, giving an overall trap success of 6.6%. Hantavirus antibody was detected in 30 of 555 Oligoryzomys longicaudatus (reservoir of Andes virus), three of 411 Abrothrix longipilis, and one of 10 Loxodontomys micropus. Antibody prevalences in O. longicaudatus were 13.7% in spring 1996, 59.3% in summer 1996, 2.1% in autumn 1997, 12.4% in winter 1997 and 3.1% in spring 1997. A much higher antibody prevalence (33%) was found during trapping around the residence of an HPS case patient. Higher prevalences were found in older male O. longicaudatus. There was no apparent correlation of antibody prevalence with rodent population density, or of rodent population density or antibody prevalence with numbers of human cases. For an HPS case that occurred in our study area in 1997, we identified the probable rodent reservoir and likely site of exposure by matching the genetic sequences of virus obtained from a rodent and the HPS case patient.

Animals↗
PubMed2001

Specific inhibition of human immunodeficiency virus type 1 (HIV-1) integration in cell culture: putative inhibitors of HIV-1 integrase.

To study the effect of potential human immunodeficiency virus type 1 (HIV-1) integrase inhibitors during virus replication in cell culture, we used a modified nested Alu-PCR assay to quantify integrated HIV DNA in combination with the quantitative analysis of extrachromosomal HIV DNA. The two diketo acid integrase inhibitors (L-708,906 and L-731,988) blocked the accumulation of integrated HIV-1 DNA in T cells following infection but did not alter levels of newly synthesized extrachromosomal HIV DNA. In contrast, we demonstrated that L17 (a member of the bisaroyl hydrazine family of integrase inhibitors) and AR177 (an oligonucleotide inhibitor) blocked the HIV replication cycle at, or prior to, reverse transcription, although both drugs inhibited integrase activity in cell-free assays. Quercetin dihydrate (a flavone) was shown to not have any antiviral activity in our system despite reported anti-integration properties in cell-free assays. This refined Alu-PCR assay for HIV provirus is a useful tool for screening anti-integration compounds identified in biochemical assays for their ability to inhibit the accumulation of integrated HIV DNA in cell culture, and it may be useful for studying the effects of these inhibitors in clinical trials.

Acetoacetates↗
PubMed2001

Streptococcus pneumoniae PstS production is phosphate responsive and enhanced during growth in the murine peritoneal cavity.

Differential display-PCR (DDPCR) was used to identify a Streptococcus pneumoniae gene with enhanced transcription during growth in the murine peritoneal cavity. Northern dot blot analysis and comparative densitometry confirmed a 1.8-fold increase in expression of the encoded sequence following murine peritoneal culture (MPC) versus laboratory culture or control culture (CC). Sequencing and basic local alignment search tool analysis identified the DDPCR fragment as pstS, the phosphate-binding protein of a high-affinity phosphate uptake system. PCR amplification of the complete pstS gene followed by restriction analysis and sequencing suggests a high level of conservation between strains and serotypes. Quantitative immunodot blotting using antiserum to recombinant PstS (rPstS) demonstrated an approximately twofold increase in PstS production during MPC from that during CCs, a finding consistent with the low levels of phosphate observed in the peritoneum. Moreover, immunodot blot and Northern analysis demonstrated phosphate-dependent production of PstS in six of seven strains examined. These results identify pstS expression as responsive to the MPC environment and extracellular phosphate concentrations. Presently, it remains unclear if phosphate concentrations in vivo contribute to the regulation of pstS. Finally, polyclonal antiserum to rPstS did not inhibit growth of the pneumococcus in vitro, suggesting that antibodies do not block phosphate uptake; moreover, vaccination of mice with rPstS did not protect against intraperitoneal challenge as assessed by the 50% lethal dose.

ATP-Binding Cassette Transporters↗
PubMed2001

Vaccination with attenuated simian immunodeficiency virus by DNA inoculation.

Delivering attenuated lentivirus vaccines as proviral DNA would be simple and inexpensive. Inoculation of macaques with wild-type simian immunodeficiency virus strain mac239 (SIV(mac239)) DNA or SIV(mac239) DNA containing a single deletion in the 3' nef-long terminal repeat overlap region (nef/LTR) led to sustained SIV infections and AIDS. Injection of SIV(mac239) DNA containing identical deletions in both the 5' LTR and 3' nef/LTR resulted in attenuated SIV infections and substantial protection against subsequent mucosal SIV(mac251) challenge.

Amino Acid Sequence↗
PubMed2001

The history of modern psychiatry in India, 1858-1947.

This article presents an introduction to the history of Indian psychiatry. It suggests that this history can be divided into four main periods, 1795 to 1857, 1858 to 1914, 1914 to 1947 and 1947 to the present day. The focus of the piece is on the periods 1858-1914 and 1914-1947, as it traces the main trends and developments of the colonial era and argues that the foundations of modern psychiatry in India were laid down in the period of British rule. A brief consideration of the post-Independence period suggests that the patterns established in the years of British rule have continued to influence the psychiatric system of modern India. Research for these conclusions is based on extensive archival work in Indian mental health institutions and in Indian records offices, as well as work conducted at the National Library of Scotland in Edinburgh and at the India Office Library, the Wellcome Institute Library and the London School of Hygiene and Tropical Medicine.

Colonialism↗
PubMed2001

Serologic evidence of hantavirus infection in sigmodontine rodents in Mexico.

Antibodies to hantaviruses in two species of sigmodontine rodents (Peromyscus maniculatus and Reithrodontomys sumichrasti) collected in central Mexico are reported. Peromyscus maniculatus, a common species throughout much of Mexico, is the reservoir of Sin Nombre virus (SNV), the etiologic agent of the great majority of cases of hantavirus pulmonary syndrome (HPS) in North America. Although the identity of the virus detected in P. maniculatus in Mexico could not be determined by these serologic results, our findings suggest that SNV may occur throughout the range of P. maniculatus in North America. If true, the failure to identify HPS in Mexico is not due to the absence of pathogenic hantaviruses in Mexico.

Animals↗
PubMed2001

Infectivity of wild-type and deleted proviral SIV DNA.

Live attenuated lentiviruses are potentially effective candidate HIV vaccines; however, delivery of these viruses in the field would be problematic. Delivery of attenuated lentiviruses as proviral DNA would be a simple means of immunization, but the efficiency of this method of delivery is not known. In this study, macaques were readily infected following inoculation of plasmid DNA encoding proviral simian immunodeficiency virus (SIVmac239), whether given i.m. (300 microg) or epidermally (15 microg), with all four animals succumbing to AIDS at a mean of 26 weeks following inoculation. Using a human skin explant model, we found that the 50% infectious dose (ID50) of proviral SIV or HIV-1 plasmid may be as low as 1 microg when delivered to skin by gold particle bombardment using a gene gun. An infectious proviral clone of SIV mac239 with a 105 bp deletion in the 3' nef/LTR overlap region was engineered (SIVsbbc delta3), analogous to the initial common nef/LTR deletion in HIV-1 strains isolated from an Australian cohort of long-term slow-progressors. Two further macaques were also readily infected with SIVsbbc delta3 after i.m. injection of 300 microg of highly purified plasmid DNA. Unexpectedly, in one macaque inoculated with SIVsbbc delta3 DNA, SIV strains isolated three to six weeks after infection had completely repaired the nef/LTR deletion with wild-type sequence, and eventually progressed to AIDS. The mechanism used to rebuild this deletion with wild-type sequence, presumably derived from an intact 5' LTR, is unclear, but possibilities include RNA read-through errors from the plasmid DNA and recombination with residual plasmid DNA at the inoculation site.

Animals↗
PubMed2000

Carboxyl-terminal fragments of Alzheimer beta-amyloid precursor protein accumulate in restricted and unpredicted intracellular compartments in presenilin 1-deficient cells.

Absence of functional presenilin 1 (PS1) protein leads to loss of gamma-secretase cleavage of the amyloid precursor protein (betaAPP), resulting in a dramatic reduction in amyloid beta peptide (Abeta) production and accumulation of alpha- or beta-secretase-cleaved COOH-terminal fragments of betaAPP (alpha- or beta-CTFs). The major COOH-terminal fragment (CTF) in brain was identified as betaAPP-CTF-(11-98), which is consistent with the observation that cultured neurons generate primarily Abeta-(11-40). In PS1(-/-) murine neurons and fibroblasts expressing the loss-of-function PS1(D385A) mutant, CTFs accumulated in the endoplasmic reticulum, Golgi, and lysosomes, but not late endosomes. There were some subtle differences in the subcellular distribution of CTFs in PS1(-/-) neurons as compared with PS1(D385A) mutant fibroblasts. However, there was no obvious redistribution of full-length betaAPP or of markers of other organelles in either mutant. Blockade of endoplasmic reticulum-to-Golgi trafficking indicated that in PS1(-/-) neurons (as in normal cells) trafficking of betaAPP to the Golgi compartment is necessary before alpha- and beta-secretase cleavages occur. Thus, although we cannot exclude a specific role for PS1 in trafficking of CTFs, these data argue against a major role in general protein trafficking. These results are more compatible with a role for PS1 either as the actual gamma-secretase catalytic activity or in other functions indirectly related to gamma-secretase catalysis (e.g. an activator of gamma-secretase, a substrate adaptor for gamma-secretase, or delivery of gamma-secretase to betaAPP-containing compartments).

Alzheimer Disease↗
PubMed2000

An epidemic without illness. Using dna markers to model infection.

PURPOSE: Combining molecular biology with infection control interventions can increase compliance and allow objective measurement of effectiveness. We developed a group of PCR detectable non-infectious DNA markers that can be used to model infection and provide immediate feedback on hygiene practices in institutional settings. In previous studies, we illustrated that the markers were spread in the environment in the same manner as infectious particles.METHODS: We are conducting a prospective study in 10 child care centers in order to 1) confirm that the DNA markers are valid surrogates for bacteria and viruses; 2) identify specific foci of contamination and modes of transmission; 3) illustrate the effectiveness of infection control programs utilizing the DNA markers. Centers are randomized to receive an interactive educational infection control intervention or a standard immunization intervention. The DNA markers are introduced into the center and the rate of dispersion of the DNA markers is compared with directly observed changes in hygiene behavior among the staff.RESULTS: Initial results indicate that the markers can be removed mechanically by hand washing and that common over-the-counter cleaners are effective in inactivating the markers. Toys, countertops and doorknobs appear to be more important as infectious reservoirs than brief casual contact. Data from the prospective study will be available prior to September, 2000.CONCLUSIONS: This novel approach utilizing an objective measurement will be used to identify the interaction between behavior and environmental reservoirs of infection and drive future strategies for infection control.

Journal Article↗