Cellular and humoral immune responses to varicella-zoster virus in immunocompromised patients during and after varicella-zoster infections.

Humoral and cell-mediated immune responses to varicella-zoster (V-Z) virus were assessed in patients during and after V-Z infections. Ongoing V-Z infections was associated with minimal cellular immunity but not necessarily with poor humoral immunity. Recovery from V-Z infection was associated with a vigorous cellular immune response. Cell-mediated immunity to V-Z virus was demonstrable for years after varicella, but responses were lower in immunocompromised patients than in normal individuals.     

Secretory processes in follicular cells of the bat thyroid. III. The occurrence of extracellular vesicles and colloid droplets during arousal from hibernation

Ultrastructural changes that occur in follicular cells of the bat thyroid gland just prior to, and immediately after arousal from hibernation are discussed in relation to the known changes which occur in thyroid function during arousal from hibernation. The most distinctive ultrastructural change that takes place just before emergence from hibernation is the occurrence, extracellularly, of concentrations of small vesicles lying in the colloid near the cell's apical plasma membrane. Similar accumulations of vesicles are absent in the apical cytoplasm of the follicular cell. Other principal changes from the early hibernating state found at this time are an increase in the number of apical vacuoles, dense granules and multivesicular bodies. These changes are followed at arousal itself by the appearance of large numbers of intracytoplasmic colloid droplets, often intimately associated with dense granules. An unusual feature of these follicular cells is that although they are rich in colloid droplets, apical pseudopods cannot be found.     

Studies of biological factors associated with the inheritance of schizophrenia: A selective review

Although a familial component to schizophrenia has been established through several familial, twin and adoption studies, an inherited biological factor has yet to be established. Efforts to define clinical familial subtypes of schizophrenia have generally been unsuccessful, although recent data from our study population of pairs of siblings with schizophrenia suggests that schizophrenia with recurrent episodes of major depression may define one such group.

There have only been a few biological traits consistently found to be associated with schizophrenia and also found to be heritable. These findings (e.g. measures of monomine metabolism, brain structural morphology, neurophysiological markers, and protein polymorphisms) are reviewed in the present chapter. The proportion of patients with any of the noted abnormalities never approaches 100%, nor have any been found to be specific to schizophrenia. Research into the biogenetics of schizophrenia is clearly just beginning.     

Bone morphogenetic protein regulation of enteric neuronal phenotypic diversity: relationship to timing of cell cycle exit

The effects of bone morphogenetic protein (BMP) signaling on enteric neuron development were examined in transgenic mice overexpressing either the BMP inhibitor, noggin, or BMP4 under control of the neuron specific enolase (NSE) promoter. Noggin antagonism of BMP signaling increased total numbers of enteric neurons and those of subpopulations derived from precursors that exit the cell cycle early in neurogenesis (serotonin, calretinin, calbindin). In contrast, noggin overexpression decreased numbers of neurons derived from precursors that exit the cell cycle late (gamma-aminobutyric acid, tyrosine hydroxylase [TH], dopamine transporter, calcitonin gene-related peptide, TrkC). The numbers of TH- and TrkC-expressing neurons were increased by overexpression of BMP4. These observations are consistent with the idea that phenotypic expression in the enteric nervous system (ENS) is determined, in part, by the number of proliferative divisions neuronal precursors undergo before their terminal mitosis. BMP signaling may thus regulate enteric neuronal phenotypic diversity by promoting the exit of precursors from the cell cycle. BMP2 increased the numbers of TH- and TrkC-expressing neurons developing in vitro from immunoselected enteric crest-derived precursors; BMP signaling may thus also specify or promote the development of dopaminergic TrkC/NT-3-dependent neurons. The developmental defects in the ENS of noggin-overexpressing mice caused a relatively mild disturbance of motility (irregular rapid transit and increased stool frequency, weight, and water content). Although the function of the gut thus displays a remarkable tolerance for ENS defects, subtle functional abnormalities in motility or secretion may arise when ENS defects short of aganglionosis occur during development.     

Rates of response,euthymia and remission in two placebo-controlled olanzapine trials for bipolar mania

Objective:  Clinically meaningful recovery from acute mania may not be captured by conventionally reported response categorizations. We defined new and stringent criteria for remission in bipolar mania. Using a cohort of patients with acute mania randomized to treatment with either olanzapine or placebo, we contrasted remission rates to findings using previously reported but more lenient categorical outcome measures of response and euthymia.
Methods:  We pooled and reanalyzed results through 3 weeks from two published randomized double-blind trials of olanzapine versus placebo for treating acute bipolar mania ( 1, 2 ). Response was previously defined as ≥ 50% decrease from baseline to endpoint total Young Mania Rating Scale ( 3 ) (Y-MRS) scores, and euthymia as an endpoint total Y-MRS score of ≤ 12. In this report, remission required an endpoint total Y-MRS score of ≤ 7, and an endpoint total Hamilton Depression Rating Scale, (HAM-D21) ( 4 ) score of ≤ 7 and an endpoint Clinical Global Impression Scale – Bipolar version, CGI-BP ( 5 ), overall severity score of ≤ 2.
Results:  Olanzapine treated subjects achieved statistically significantly greater rates of clinical response, euthymia and remission than those assigned to placebo, 55% versus 29.5%, 50% versus 27%, and 18% versus 7%, respectively.
Conclusions:  Olanzapine monotherapy resulted in discernable clinical improvements in mania in over 50% of subjects and just under 20% of subjects achieved a near complete resolution of manic and accompanying depressive symptoms after 3 weeks of treatment. Full remission is an important but potentially elusive goal during short-term management of acute mania.     

Nonprogression of coronary artery atherosclerosis in homozygous familial hypercholesterolemia after 31 months of repetitive plasma exchange

The effects of plasma exchange performed every two weeks for 31 months in combination with diet and drug therapy were studied in a patient with receptor-defective homozygous familial hypercholesterolemia. Coronary angiography performed three years prior to commencing plasma exchange was compared to angiography 31 months after starting the program. Comparison of the angiograms taken six years apart showed no progression of coronary atheroma in the main left coronary artery in which a 30% narrowing was originally seen. An internal mammary artery-coronary artery bypass remained widely patent and showed no development of atherosclerosis. Plasma cholesterol levels were reduced 46% by plasma exchange, diet and drug compared to diet and drug alone. Achilles tendon xanthoma diminished significantly. It appears that plasma exchange combined with diet and drug therapy, while not producing regression of existing atheromatous lesions, does retard or prevent further progression.     

Functional deletion of different Ly-1 T-cell-inducer subset activities by Ly-2 suppressor T lymphocytes.

T-suppressor-cell activity was analyzed by use of an intermediate culture system that allows the study of T-cell interactions in the absence of concomitant inducer effects on B cells. Activated suppressor T cells were incubated with their potential target cells [immune Ly-1+,Ly-2- (Ly-1) cells] for 24-48 hr, and then the Ly-1 cells were reisolated by removing the suppressor cells with an appropriate antiserum (Ly-2). The functional consequences of the interactions that occurred during the incubation period were then assessed. Suppressor cells deleted the functional activity of two inducer-T-cell subsets; the helper T cell, which induces B-cell production of antibody, and the T cell that induces Ly2+ T suppressor cells. This latter activity is more sensitive to suppression than is the former. As suppressor T cells inactivate the cells that are responsible for their activity (i.e., their specialized Ly-1 inducer cells), a form of negative regulation of suppressor-T-cell activity, in which the down regulation of suppressor cells is effected by their removal of their own inducer cells, can be postulated. In addition, these findings show that clonal deletion and active suppression need not be mutually exclusive mechanisms of immune unresponsiveness. Suppressor cells can produce a functional deletion of immune activity that persists after they themselves are removed, for example, by antisera, or in physiological situations by the negative form of regulation postulated.     

Serum anti-Mullerian hormone levels during controlled ovarian hyperstimulation in women with polycystic ovaries with and without hyperandrogenism

BACKGROUND: Anti-Mullerian hormone (AMH) is expressed in pre- and small-antral follicles. High serum levels are found in women with polycystic ovaries (PCO), accordant with their increased content of small follicles. To evaluate the relationship between AMH, folliculogenesis and hyperandrogenism, we compared serum AMH levels between women with PCO with and without hyperandrogenism and normal controls during controlled ovarian hyperstimulation (COH). METHODS: Nineteen women with PCO and hyperandrogenism (group A), 10 women with PCO but no hyperandrogenism (group B) and 23 ovulatory women with normal ovarian morphology (group C, controls) underwent COH with the long protocol. Serum levels of AMH, estradiol, androstenedione and follicular tracking were determined before gonadotropins treatment (day 0) and every 2-4 days up to the day of HCG administration. RESULTS: AMH levels declined gradually throughout COH in the three groups, but remained higher in groups A and B compared with the controls. Significantly higher levels were found in group A compared with group B, despite comparable numbers of small follicles. Multiple regression analysis revealed that both the number of small follicles and serum androgens were correlated to AMH. CONCLUSIONS: Women with PCO have higher serum AMH levels during COH than controls. Hyperandrogenism is associated with an additional increase in AMH. It is conceivable that hyperandrogenism may reflect more severe disruption of folliculogenesis in women with PCO or may affect AMH secretion.     

Increased prooxidant production and enhanced susceptibility to glutathione depletion in HepG2 cells co-expressing HCV core protein and CYP2E1

Hepatitis C virus (HCV) and HCV core protein are hypothesized to induce hepatic oxidative stress and exacerbate injury caused by other toxins such as ethanol that induce the cytochrome P450 enzyme, CYP2E1. In the current study, the effects of HCV core protein [sequence genotype 1b, (nt 342-915)] on parameters indicative of oxidative stress were evaluated in HepG2 cells stably over expressing CYP2E1 (E47), or vector controls (C34). Stable (>10 passages) expression of HCV core protein and CYP2E1 was confirmed in clonal cell lines at the level of mRNA and immunoreactive protein. Prooxidant production, as determined by cellular oxidation of dichlorodihydrofluorescin and dihydroethidium (HE), was increased by expression of HCV core protein in the presence or absence of CYP2E1. Depletion of glutathione (GSH) with buthionine sulfoximine (BSO) enhanced prooxidant production in both C34 and E47 cells. In addition, prooxidant production was greater in BSO-treated cells expressing HCV core protein, and this effect was further enhanced in cells expressing both HCV core and CYP2E1. The CYP2E1 inhibitor, 4-methylpyrazole, could suppress increased prooxidant production in E47 cells. Finally, cells co-expressing both CYP2E1 and HCV core protein showed significantly decreased viability following GSH depletion. These studies show simultaneous expression of HCV core protein and CYP2E1 increases parameters indicative of oxidative stress as well as sensitization to cell injury induced by GSH depletion. These results support the hypothesis that enhanced injury in hepatocytes over expressing both HCV core protein and CYP2E1 is mediated by increases in oxidative stress.