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Biomedical subjects

M Schiff

Publications and source records attributed to M Schiff.

At least 55 records · Page 3Linked to original sources

Genetic analysis of the imperfect association of H-2 haplotype with lupus-like autoimmune disease.

Unlike parental New Zealand Black (NZB) or New Zealand White (NZW) mice, (NZB x NZW)F1 mice exhibit a lupus-like disease characterized by high serum levels of IgG anti-nuclear antibodies and a fatal immune complex glomerulonephritis. Previous results from studying [(NZB x NZW)F1 x NZB] backcross mice indicated that the NZW major histocompatibility complex (MHC) or gene(s) closely linked to this locus provides the major dominant NZW genetic contribution to the F1 disease. A surprising feature of the results was the 12% frequency of discordance between the autoimmune phenotype and the presence of the NZW H-2z haplotype. In the current study, we attempted to precisely define the position of the NZW gene(s) required for lupus-like renal disease by mapping genes in individual backcross mice that are both centromeric and telomeric to the MHC and then correlating genotypes for each locus with disease. The data indicate that an adjacent NZW locus does not provide a more accurate correlation with the autoimmune phenotype compared with MHC genes themselves. Thus, the imperfect association of MHC haplotype with disease in this murine model is not explained by genetic recombination with linked genes. These data may provide insight into the mechanisms by which MHC antigens increase the probability of developing autoimmune disease and may help explain the difficulty of defining MHC relationships in human systemic lupus erythematosus.

Alleles↗

Acquired immunodeficiency syndrome, a complication of cardiothoracic surgery.

We identified 13 patients who contracted acquired immunodeficiency syndrome or human immunodeficiency virus-related disease after a cardiothoracic operation. The operations were performed between January 1981 and November 1984, and the diagnosis of human immunodeficiency virus-related disease was established from 26 to 54 months after operation. The survival time from diagnosis ranged from 8 days to 14 months in the 10 patients who have died. A clinical illness developed in three of the patients immediately postoperatively that was consistent with primary human immunodeficiency virus mononucleosis. The clinical features included a wide variety of opportunistic infections, but an abnormally high percentage of the patients first showed symptoms of dementia or neoplastic disease. In many patients, the diagnosis was not suspected for a prolonged period of time. On the basis of the prolonged incubation period, the incidence of this disease is likely to increase for several more years.

Acquired Immunodeficiency Syndrome↗

Behavioral sequelae of physical and/or sexual abuse in adolescents.

In a survey of 500 admissions to a short-term residential chemical dependency treatment center for adolescents (ages 12 to 18), 150 adolescents (30%) had been identified as victims of physical and/or sexual abuse. While the abused group had a higher incidence of prior social service and mental health intervention, extraordinarily 68% of these abuse cases had not been reported by children, family, or interviewers prior to the adolescents having entered the chemical dependency residential treatment facility. This chemically dependent, previously abused group was differentiated from a comparison group of nonabused, chemically dependent adolescents, and a second comparison group of nonabused, nonchemically dependent adolescents. Results indicated a higher incidence of acting out behavior, runaways, legal involvement and sexual promiscuity within the abused group.

Adaptation, Psychological↗

Injection of low-dose antigen attenuates the response to subsequent bronchoprovocative challenge.

Injection of low-dose antigen on a co-seasonal basis has been proposed as an alternative to conventional immunotherapy in allergic disorders. Few studies of efficacy have been attempted, and available data do not support the use of this technique. We evaluated the effect of low-dose antigen injection in 21 subjects with histories of asthma, after exposure to animal antigen. Each subject was injected with low-dose animal antigen, as determined by skin test end point titration, or with placebo. Twenty minutes after the injection, bronchoprovocative challenge was performed with the use of the same antigen. The provocative dose 20% (PD20), FEV1 after antigen injection, was 28.52 +/- 1.74, was compared to 6.50 +/- 1.15 after placebo injection (p less than 0.01). This experiment was repeated after pretreatment of patients with indomethacin. The protective effect of antigen injection was abolished. In a third experiment, the PD20, FEV1 for methacholine, was 10.74 breath units (BU) after antigen injection and 6.84 BU after placebo injection (PD less than 0.05). Low-dose antigen injection causes rapid reduction of bronchial sensitivity to inhaled antigen and methacholine. This effect is abolished by treatment with indomethacin.

Adult↗

Vascular complications in renal allografts: detection with duplex Doppler US.

Renal allografts are subject to many vascular complications. Over a 2-year period, 334 duplex Doppler ultrasonographic (US) examinations were performed in 88 renal allograft recipients. Vascular occlusion on the basis of severe vascular rejection was documented in ten patients (11.4%) for a sensitivity and specificity of 100%. Seven patients, for whom there was clinical and Doppler US evidence for renal artery stenosis, underwent angiography. A significant stenosis was confirmed and treated by angioplasty in four patients; one had an insignificant stenosis in an accessory artery, one had kinking of the renal vessels, and another had normal findings. The most reliable criteria for stenosis were a high-velocity jet exceeding 7.5 kHz and distal turbulence. One arteriovenous fistula was diagnosed by the presence of an intrarenal high-velocity jet. Duplex Doppler US is a useful, noninvasive, and portable initial procedure with which to screen patients for vascular complications of renal transplantation.

Adult↗

Left ventricular diastolic function in weight lifters.

Concentric left ventricular (LV) hypertrophy and asymmetric septal hypertrophy have both been described in weight lifters, but diastolic filling, which is abnormal in pathologically hypertrophied ventricles, has not been investigated in such subjects. Accordingly, pulsed Doppler examination of LV inflow, M-mode and 2-dimensional echocardiography were performed in 16 competitive weight lifters and 10 age-matched male control subjects. Peak and mean filling rates were determined in milliliters per second as the product of the cross-sectional area of the mitral anulus and the Doppler-derived peak early and mean transmitral inflow velocities, respectively. Rapid filling index was defined as peak filling rate divided by mean filling rate. Flow velocity integrals of the early and atrial diastolic filling phases were also measured. LV end-diastolic volume and ejection fraction were measured using 2-dimensional echocardiography. Weight lifters had significantly higher LV end-diastolic volume (181 +/- 50 vs 136 +/- 40 ml, p less than 0.05) and dimension (5.6 +/- 0.6 vs 5.1 +/- 0.5 cm, p less than 0.05), and posterior wall thickness (0.9 +/- 0.2 vs 0.8 +/- 0.1, p less than 0.05); however, after correction for body surface area there was no significant difference in these values. Weight lifters had significantly higher LV mass (241 +/- 70 vs 165 +/- 29, p less than 0.02) and LV mass index (114 +/- 29 vs 87 +/- 15 g/m2, p less than 0.05). There was no significant difference between the weight lifters and control subjects in rapid filling index, early to late integral ratio or ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Renal adenocarcinoma in young adults.

Survival following the diagnosis of renal adenocarcinoma in a group of young adults, twenty to forty years of age, was distinctly better than that found in adults over age forty. This disparity could not be accounted for by a larger proportion of younger patients with early stage disease, nor by a greater percentage of non-cancer deaths in the older group. Perhaps a more favorable host-tumor immunologic balance is present in younger individuals.

Adult↗

Opioid and neurotransmitter regulation of pituitary gonadotropin-releasing hormone (GnRH) receptors in the ovariectomized estradiol-treated rat: role of altered GnRH secretion.

An acute transient fall in the number of pituitary GnRH receptors (GnRH-R) is observed before the preovulatory gonadotropin surge in cycling rats and before the afternoon daily gonadotropin surge in ovariectomized estradiol-treated rats. In the latter model, this fall can be reproduced by administration of the opioid antagonist naloxone, whereas the opioid agonist morphine acutely increases GnRH-R. In this study we investigated the mechanisms of this opioid effect and examined the effects of other neurotransmitter substances on modulation of pituitary GnRH-R. Administration of the dopaminergic agonists bromocriptine and L-dopa or the alpha-adrenergic receptor blocker phenoxybenzamine elevated GnRH-R acutely from average basal values of 240 +/- 22 and 254 +/- 21 fmol/mg protein to maximal values of 374 +/- 49, 441 +/- 67 and 461 +/- 75 fmol/mg, respectively, whereas the alpha-adrenergic agonist clonidine transiently decreased GnRH-R to 186 +/- 19 fmol/mg. Placement of radiofrequency lesions in the mediobasal hypothalamus or pretreatment with anti-GnRH serum completely abolished the ability of both morphine and naloxone to modulate the number of GnRH-R. These data indicate that the opioid-induced modulation of pituitary GnRH-R requires an intact hypothalamus and that both dopaminergic and alpha-adrenergic neurotransmitter systems may be involved. The final step of this action probably involves acute modulation of GnRH secretion (altered frequency and/or amplitude), which results in acute transient changes in the number of pituitary GnRH-R.

Animals↗

Immunologic aspects of otologic disease: an overview.

The immunologic explosion has now reached the field of otology. By having better techniques to measure the changes at cellular and molecular levels, it is now possible to devise experiments to show morphologic anatomic changes as well as functional changes. The demonstration in 1980 (M.S.) that tympanosclerosis could be induced immunologically represents a concrete advancement in immunologic thinking in conceptualization of otologic disease. In 1974, one of the authors (M.S.) published work dealing with the treatment of vasculitis of immunologic origin for sudden hearing loss. This was aimed at inhibiting the complement cascade from starting its destructive action. Recently, the immunologic challenge in animals demonstrated by changes in the inner ear was shown by one of the authors (T.J.Y.). Such changes were compatible with labyrinthine hydrops, or Meniere's disease, otosclerosis, and sensorineural hearing loss and vestibular dysfunction.

Cholesteatoma↗

Regulation of pituitary gonadotropin-releasing hormone receptors by pulsatile gonadotropin-releasing hormone injections in male rats. Modulation by testosterone.

The pattern of the gonadotropin-releasing hormone (GnRH) stimulus is critically important in the regulation of pituitary gonadotropin secretion and continuous infusions down-regulate secretion while intermittent pulses maintain luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responsiveness. We examined the effects of pulsatile GnRH administration on pituitary GnRH receptors (GnRH-R) and gonadotropin secretion in the presence of physiological concentrations of testosterone (T) to elucidate the mechanisms and sites of action of GnRH and T on the pituitary gonadotroph. Castrate male rats received one, two, or four testosterone (T) implants (serum T concentrations of 1.1, 2.4, and 5.2 ng/ml, respectively) to suppress endogenous GnRH secretion. Subsequently, intracarotid pulse injections of GnRH (5-250 ng/pulse) or saline in controls were given every 30 min for 48 h, after which gonadotropin responses and pituitary GnRH-R were measured. In control rats, the T implants prevented the rise in GnRH-R that was seen in castrates (empty implant--600 fmol/mg protein) and maintained receptors at the level that was present in intact animals (300 fmol/mg). Pulsatile GnRH administration increased GnRH-R in castrate T-implanted rats, but the response was dependent on the serum T concentration. With one T implant, increasing GnRH doses per pulse stimulated GnRH-R in a linear manner and the maximum receptor concentration (703 +/- 99 fmol/mg) was seen after the 250 ng GnRH dose. In the presence of two T implants, GnRH-R was maximal (705 +/- 45 fmol/mg) after the 25-ng dose and higher doses did not increase receptors above control values. With four T implants, GnRH doses of 5 ng induced a maximum response, 17-50 ng/pulse did not increase GnRH-R, but receptors were again increased by the 250-ng dose (633 +/- 86 fmol/mg). After 48 h of pulsatile GnRH administration there was no correlation between the number of GnRH-R and LH responses to GnRH. In rats with one or two T implants, LH responses were absent after all but the 250-ng doses. In contrast, LH responsiveness was not impaired in the presence of four implants. Thus, low dose GnRH pulses down-regulate LH secretion by an action at a post GnRH-R site, and this effect is regulated by testosterone. The results show that GnRH, given in a pulsatile manner, regulates its own receptor, and physiological increases in serum T produce a 50-fold increase in the sensitivity of GnRH-R stimulation by GnRH.

Animals↗