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Biomedical subjects

J Pryor

Publications and source records attributed to J Pryor.

At least 19 recordsLinked to original sources

Productive infection of T cells in lymphoid tissues during primary and early human immunodeficiency virus infection.

Current models suggest that during human immunodeficiency virus type 1 (HIV-1) transmission virions are selected that use the CCR5 chemokine receptor on macrophages and/or dendritic cells. A gradual evolution to CXCR4 chemokine receptor use causes a shift in the proportion of productively infected cells to the CD4 cell population. Productively infected cells during acute and early infection in lymphoid tissue were assessed, as well as the impact of productive infection on the T cell population in 21 persons who had biopsies performed on days 2-280 after symptoms of acute HIV-1 seroconversion. Even in the earliest stages of infection, most productively infected cells were T lymphocytes. There were sufficient infected cells in lymphoid tissue (LT) to account for virus production and virus load in plasma. Despite the relatively high frequency of productively infected cells in LT, the impact on the size of the T cell population in LT at this stage was minor.

CD4-Positive T-Lymphocytes↗

Rapid accumulation of human immunodeficiency virus (HIV) in lymphatic tissue reservoirs during acute and early HIV infection: implications for timing of antiretroviral therapy.

The follicular dendritic cell network (FDC) in lymphoid tissues (LTs) is the major site of human immunodeficiency virus (HIV) storage in presymptomatic and late stages of disease. However, little is known about the rate of virus accumulation during the acute and early stages. In situ hybridization and quantitative image analysis were used to determine the amount of virus bound to the FDC network during the first year of infection. The FDC pool was already >7.0 log10 copies of HIV RNA/g LT in the first year, and 2 patients biopsied within 2-4 days of symptom onset had 7.3 and 8.2 log10 copies of HIV RNA/g LT, respectively. There was no correlation between duration of infection and accumulation of HIV into the FDC network. These data suggest that a large pool of infectious virus is established soon after infection and that initiation of antiretroviral therapy when symptoms of primary HIV infection are recognized is unlikely to prevent substantial accumulation of virus in the FDC network.

Acute Disease↗

Defining regions of the Y-chromosome responsible for male infertility and identification of a fourth AZF region (AZFd) by Y-chromosome microdeletion detection.

Cytogenetic and molecular deletion analyses of azoospermic and oligozoospermic males have suggested the existence of AZoospermia Factor(s) (AZF) residing in deletion intervals 5 and 6 of the human Y-chromosome and coinciding with three functional regions associated with spermatogenic failure. Nonpolymorphic microdeletions in AZF are associated with a broad spectrum of testicular phenotypes. Unfortunately, Sequence Tagged Sites (STSs) employed in screening protocols range broadly in number and mapsite and may be polymorphic. To thoroughly analyze the AZF region(s) and any correlations that may be drawn between genotype and phenotype, we describe the design of nine multiplex PCR reactions derived from analysis of 136 loci. Each multiplex contains 4-8 STS primer pairs, amplifying a total of 48 Y-linked STSs. Each multiplex consists of one positive control: either SMCX or MIC2. We screened four populations of males with these STSs. Population I consisted of 278 patients diagnosed as having significant male factor infertility: either azoospermia, severe oligozoospermia associated with hypogonadism and spermatogenic arrest or normal sperm counts associated with abnormal sperm morphology. Population II consisted of 200 unselected infertile patients. Population III consisted of 36 patients who had previously been shown to have aneuploidy, cytological deletions or translocations involving the Y-chromosome or normal karyotypes associated with severe phenotype abnormalities. Population IV consisted of 920 fertile (control) males. The deletion rates in populations I, II and III were 20.5%, 7% and 58.3%, respectively. A total of 92 patients with deletions were detected. The deletion rate in population IV was 0.87% involving 8 fertile individuals and 4 STSs which were avoided in multiplex panel construction. The ability of the nine multiplexes to detect pathology associated microdeletions is equal to or greater than screening protocols used in other studies. Furthermore, the data suggest a fourth AZF region between AZFb and AZFc, which we have termed AZFd. Patients with microdeletions restricted to AZFd may present with mild oligozoospermia or even normal sperm counts associated with abnormal sperm morphology. Though a definitive genotype/phenotype correlation does not exist, large deletions spanning multiple AZF regions or microdeletions restricted to AZFa usually result in patients with Sertoli Cell Only (SCO) or severe oligozoospermia, whereas microdeletions restricted to AZFb or AZFc can result in patients with phenotypes which range from SCO to moderate oligozoospermia. The panel of nine multiplexed reactions, the Y-deletion Detection System (YDDS), provides a fast, efficient and accurate method of assessing the integrity of the Y-chromosome. To date, this study provides the most extensive screening of a proven fertile male population in tandem with 514 infertile males, derived from three different patient selection protocols.

Female↗

Prosthesis implantation after radial free flap phalloplasty in patients with bladder exstrophy.

METHODS: Inflatable penile prosthesis were implanted into sensate radial free-flap phalloplasties in two adult patients with bladder exstrophy. RESULTS: Neither patient reported loss of sensation, and both were able to inflate the prosthesis and engage in sexual intercourse three months later. CONCLUSION: The construction of a functional neophallus is well described however has not previously been reported in exstrophy patients who are suited to this procedure due to the presence of crura, and the absence of a neourethra. Scarring from previous reconstructive procedures however may make implantation difficult, and long-term follow up is required to evaluate this procedure in patients with bladder exstrophy.

Adult↗

Venous anomalies and associated lesions.

Developmental venous anomalies (DVAs) of the central nervous system are an exaggeration of the normal venous collector system, not a vascular lesion. They may be associated with many vascular and nonvascular processes with the nervous system including tumors, demyelinating lesions, arteriovenous malformations (AVMs), dural AVMs, cavernous malformations, and vascular lesions of the head, face, and eye. The instigating factors involved are not completely understood. The primary clinical significance of DVAs is that planned or inadvertent occlusion during treatment of associated lesions frequently leads to venous infarction of the surrounding normal brain.

Central Nervous System Diseases↗

Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm.

The association of abnormal spermatogenesis in men with Y chromosome deletions suggests that genes important for spermatogenesis have been removed from these individuals. Recently, genes encoding two putative RNA-binding proteins (RBM and DAZ/SPGY) have been mapped to two different regions of the human Y chromosome. Both of these genes encode proteins that contain a single RNA recognition motif and a (different) internally repeating sequence. Y-linked RBM homologues are found in all mammalian species. We have raised an antiserum to RBM and used it to show that RBM is a nuclear protein expressed in fetal, prepubertal, and adult male germ cells. The distribution of RBM protein in the adult correlates with the pattern of transcriptional activity in spermatogenesis, suggesting that RBM is involved in the nuclear metabolism of newly synthesized RNA. RBM sequences are found on both arms of the Y chromosome making genotype-phenotype correlations difficult for this gene family. To address the location of the functional genes and the consequences of their deletion, we examined a panel of men with Y chromosome deletions and known testicular pathologies using this antiserum. This approach enabled us to map a region of the Y chromosome essential for RBM expression. In the absence of detectable RBM expression we see stages of germ cell development up to early meiosis, but not past this point into the haploid phase of spermatogenesis.

Adult↗

A senior volunteer/home care agency national collaboration: assessment of the partnership.

This research has focused on a partnership between a private sector home health care entity, the Visiting Nurse Associations of America (VNAA) and the public sector Senior Companion Program (SCP) of the domestic volunteer agency now a part of the Corporation for National and Community Service. This research examined the partnerships between the two agencies in 18 local demonstration sites in order to assess how a home health agency worked. Specific areas reviewed were administration of the partnership, communication patterns between the agencies, areas of conflict, the future of the liaison, and how effectively volunteer performance matched original expectations.

Aged↗

Comparison of SUZI and ICSI for severe male factor.

We compare the results of subzonal insemination (SUZI) and intracytoplasmic sperm injection (ICSI) carried out between February 1993 and end of August 1994. A total of 232 couples underwent 302 cycles of micro-assisted fertilization (79 patients had SUZI for a total of 93 cycles, 153 patients ICSI for a total of 209 cycles). The indications for treatment were obstructive azoospermia in 35 cycles, ejaculatory failure with severely low sperm count in 7 cycles, and failure of fertilization in a previous IVF cycle or less than 10% of oocytes fertilized in 87 cycles. In 173 cycles the indication for treatment was a poor semen parameter. Patients undergoing ICSI had significantly higher fertilization rates [43 (728/1692) versus 22.3% (151/ 676), chi 2 = 86.308, P < 0.0001], better chances of embryo transfer [95 (199/209) versus 73% (68/93), chi 2 = 30.671, P < 0.001], and greater numbers of embryos transferred (2.4 +/- 0.9 versus 1.6 +/- 1.2 F = 42, P < 0.0001) than patients who had SUZI. Eighteen patients became pregnant following the SUZI procedure, a pregnancy rate of 19% per egg collection, compared with 28% for those who underwent the ICSI procedure, where 58 out of 209 became pregnant. The pregnancy rate was similar in those who underwent embryo transfer, whether they had ICSI or SUZI (29.2 and 28.6% respectively). Overall, the pregnancy rate doubled with each number of embryos transferred, so it was 8.9% when one embryo was transferred, which increased to 18.3% when two embryos were transferred, and this rose to 37.7% when three embryos were transferred. There was no significant difference in the pregnancy wastage rate between SUZI and ICSI. None of the offspring from either SUZI or ICSI showed any evidence of fetal abnormalities. Pregnancy rate was negatively correlated, with sperm progression being 36% (36/100) if progression was < 2 and 19.8% (40/202) if it was > or = 2 (chi 2 = 8.99, P < .002). ICSI therefore provides a higher number of embryos available for transfer and should be the primary treatment for severe male factor infertility.

Adult↗

Growth, development and behaviour in adolescents born small-for-gestational-age.

OBJECTIVE: To examine the effects on adolescents of being born small-for-gestational-age (SGA). METHODOLOGY: The sample are members of a cohort longitudinal study in which growth, cognitive development and behaviour are being studied into adulthood. Ninety-one SGA subjects were available for comparison with the rest of the sample (n = 1037) on measures of height, weight, head circumference, cognitive performance and behavioural variables to the age of 18 years old. RESULTS: SGA subjects were shorter and lighter at 18 years of age than their appropriate-for-gestational-age (AGA) counterparts despite age of onset of menarche being the same in both groups. At age 13, SGA subjects scored significantly lower than the AGA group on the WISC-R scales. They were rated by parents as having more behaviour problems at age of 15. CONCLUSIONS: SGA birth appears to be a potential problem which extends beyond childhood in its effects on growth, behaviour and cognitive performance.

Adolescent↗

Investigation of the haemolytic effects of Ancylostoma ceylanicum: observations on infected dogs in vivo and human and dog blood in vitro.

Investigations into the probable role of haemolysins in the causation of hookworm anaemia have been undertaken in living infected dogs. Secondly, the effects of living hookworms and various worm products on erythrocytes in vitro have been assessed. In dogs infected with varying numbers of A. ceylanicum, severe microcytic anaemia developed in the most heavily infected animals six weeks after infection. Erythrocytes from the latter animals showed significantly greater autohaemolysis in the presence of added glucose. When serum bilirubin and methaemalbumin, plasma haemoglobin, urinary urobilinogin and osmotic fragility of their red cells were measured, however, no evidence of haemolysis was detected. Erythrocytes from these animals appeared normal under scanning electron microscopy. In in vitro studies varying concentrations of adult worm extract had no effect on the haemolysis of either dog or human erythrocytes in the presence or absence of glucose nor on their mechanical fragility. There was no increase in 51Cr release from dog or human labelled red cells when incubated with either adult worm extract or excretory/secretory products of worms. Living adult worms caused an increase in 51Cr release from human but not dog labelled erythrocytes. Thus, the role of haemolysins in the genesis of hookworm anaemia is minimal.

Ancylostoma↗

Enhancement of uricosuric properties of indacrinone by manipulation of the enantiomer ratio.

Racemic indacrinone is a high-ceiling, relatively long-acting diuretic. Both enantiomers have uricosuric activity, but the diuretic activity resides predominantly in the (-) enantiomer. Usual therapeutic doses of racemic indacrinone have only transient uricosuric activity, so that, as with other diuretics, hyperuricemia occurs. Sixty-five healthy men participated in a multicenter, double-blind, randomized, balanced, incomplete-block study comparing the effects on plasma urate and urate clearance of indacrinone (-) enantiomer 10 mg given concomitantly with 0, 10, 20, 40, and 80 mg (+) enantiomer (10/0, 10/10, 10/20, 10/40, 10/80), as single daily doses for 7 days. Hydrochlorothiazide (HCTZ) 50 mg daily and ticrynafen (T) 250 mg daily were controls. Each subject received two of the seven treatments, so that there were 18 subjects per treatment. On days 7 to 8, morning (mean of 0-hr values on days 7 and 8), HCTZ, 10/0, 10/10, and 10/20 elevated plasma urate by 8% to 16%. 10/40 was approximately isouricemic, and 10/80 and T lowered plasma urate by 13% and 41%. There were corresponding changes in urate clearance.

Diuretics↗

Prolongation of chemotherapeutically induced remission of a syneneic murine leukemia by L-2,3,5,6-tetrahydro-6-phenylimidazo[2.1-BETA]thiazole hydrochloride.

L-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1-beta]thiazole hydrochloride (LMS), when used in concert with 1,3-bis(2-chloroethyl)-1-nitrosourea, resulted in a significantly higher percentage of long-term leukemic-free survivors. The additive effect provided by LMS treatment was evident during the immunosuppressed period induced by 1,3-bis(2-chloroethyl)-1-nitrosourea treatment and when tumor load was minimal. Treatment with LMS alone did not appear to possess any significant antitumor effect. The beneficial effect of LMS treatment may be attributable to the immunostimulatory activity reported for this drug. LMS appears to possess characteristics that make it an excellent candidate for use as an immunostimulant in cancer combined modality treatment.

Adjuvants, Immunologic↗