Liver involvement in the sulfone syndrome

A patient being treated with dapsone developed a hypersensitivity reaction with typical features of the "sulfone syndrome," including fever, malalse, and hepatitis. All abnormalities rapidly reversed with discontinuance of the dapsone regimen and institution of prednisone therapy. Hepatic involvement may be a prominent feature of the sulfone syndrome and may be of the hepatocellular or cholestatic type. Based on our review of the Food and Drug Administration reports, this syndrome appears to be relatively uncommon, but physicians need to recognize that expression of this syndrome may be incomplete. More clinical data are necessary to better define the incidence and pathogenesis of sulfone-induced liver disease.     

Altered nucleosome structure containing DNA sequences complementary to 19S and 26S ribosomal RNA in Physarum polycephalum.

The localization of DNA sequences coding for ribosomal RNA was studied by hybridization of purified ribosomal RNA to DNA from chromatin fragments prepared by limited digestion of Physarum nuclei with staphylococcal nuclease. The 32P-labeled 19S and 26S RNA hybridized to DNA from nucleosome monomers, dimers, trimers, and higher oligomers, separated by sucrose gradient centrifugation, although the level of hybridization to DNA from nucleosome fractions was less than the level of hybridization to undigested nuclear DNA. The distribution of 19S and 26S rDNA sequences in the nucleosome fractions differed from the distribution of bulk DNA in that the rDNA sequences were recovered primarily in two fractions containing monomer-sized DNA lengths (140-160 base pairs). The percentage of DNA hybridizing to 19S plus 26S RNA was greater in peak A, the more slowly sedimenting monomer peak, than in any other chromatin fraction at all stages of digestion. Peak A and monomer particles differed in protein content and distribution. The presence of ribosomal cistrons in an altered nucleosome configuration may be related to changes in functional states of rDNA chromatin.     

Expression and Regulation of mRNA for Inhibin/Activin α- and βA-Subunits in the Granulosa Layer of the Two Largest Preovulatory Follicles during the Hen Ovulatory Cycle

In order to understand the role of inhibin and activin in regulating follicular development in the hen, the steady-state mRNA levels of inhibin/activin α- and β_A-subunits in the granulosa layer of the largest (F₁) and second largest (F₂) follicles of the hen were investigated at 4-hr intervals throughout the ovulatory cycle. In addition, because it was hypothesized that luteinizing hormone (LH) regulated β_A-subunit expression, the effect ofin vivoadministration of ovine LH (oLH) on the expression of these subunits during the early- and mid-ovulatory cycle was examined. Northern blot analysis, using³²P-labeled cDNA probes of chicken inhibin/activin α- and β_A-subunits and glyceraldehyde-3-phosphate dehydrogenase (GAPDH, internal control), revealed that in the F₁follicle, the relative level of β_A-mRNA (n = 3) was low at 23.5 hr and increased (P < 0.05) at 19.5, 15.5, and 11.5 hr before the next predicted ovulation. It then decreased (P < 0.05) at 7.5 hr and was further reduced at 3.5 and 0.5 hr prior to ovulation. In the F₂follicle, β_A-mRNA was maintained at a basal level throughout the sampling period except for a brief increase (P < 0.05) at 0.5 hr before ovulation. In contrast to the β_A-subunit, inhibin α-mRNA was abundantly expressed with no significant variations throughout the ovulatory cycle in either the F₁or the F₂follicle. When oLH was injected at 18 hr before ovulation, 200 but not 100 or 50 μg/kg (n = 3 hens per dose) significantly (P < 0.05) reduced the β_A-mRNA level in the F₁follicle by 2 hr after injection compared to the control (saline). The experiment was repeated at 12 hr before ovulation and both 100 and 200 but not 50 μg/kg oLH significantly (P < 0.05) reduced the expression of β_A-subunit mRNA with no significant difference between 100 and 200 μg/kg oLH. In contrast to the β_A-subunit, inhibin α-subunit mRNA was abundantly expressed and not affected by oLH treatment. Our data indicate that the expression of inhibin/activin β_A- but not α-subunit mRNA is developmentally regulated in the granulosa layer of the two largest follicles during the hen ovulatory cycle. In addition, LH may participate, directly or indirectly, in negative regulation of the β_A-subunit.     

Expression of the F glycoprotein of respiratory syncytial virus by a recombinant vaccinia virus: comparison of the individual contributions of the F and G glycoproteins to host immunity.

A cDNA clone representing the mRNA coding sequence of the fusion glycoprotein (F) gene of human respiratory syncytial virus (RSV) was constructed and inserted into the thymidine kinase gene of vaccinia virus (WR strain) under the control of a vaccinia virus promoter. The resulting recombinant vaccinia virus, vaccinia F, expressed the F1 and F2 cleavage products (48 and 20 kDa, respectively) of the F glycoprotein in cell culture. F1 and F2 were indistinguishable from their authentic RSV counterparts with respect to glycosylation, disulfide linkage, electrophoretic mobility, cell-surface expression, and antigenic specificity. Cotton rats infected intradermally with vaccinia F developed a high titer of serum F-specific antibodies, which neutralized infectivity of RSV. This neutralizing antibody response exceeded that induced by infection of the respiratory tract with RSV and was 6-fold higher than that induced by vaccinia G, a recombinant vaccinia virus that expressed the RSV G glycoprotein gene. Immunization with vaccinia F stimulated almost complete resistance to replication of RSV in the lower respiratory tract as well as significant resistance in the upper respiratory tract. The degree of resistance conferred by vaccinia F exceeded that induced by vaccinia G.     

Physiological profiles of episodic progesterone release during the midluteal phase of the human menstrual cycle: analysis of circadian and ultradian rhythms, discrete pulse properties, and correlations with simultaneous luteinizing hormone release

To define the physiological relationships between episodic progesterone and LH release, we measured serum progesterone and LH concentrations in blood sampled at 10-min intervals for 24 h in seven young women in the midluteal phase of the menstrual cycle. The resultant time series were assessed further by Fourier transformation, Cluster analysis, and cross-correlation analysis with autoregressive modeling. These techniques permitted an examination of circadian rhythms, discrete (ultradian) pulse properties, and simultaneous or lagged correlations between progesterone and LH release. We found the following. 1) Both serum LH and progesterone concentrations had significant circadian periodicities, with similar acrophases (times of maximal nyctohemeral values). LH and progesterone also manifested multiple ultradian rhythms of similar periodicities (range, 48-241 min). 2) Discrete serum progesterone peaks occurred at a mean interpulse interval of 118 +/- 12 (+/- SE) min, had durations of 92 +/- 12 min, and had incremental amplitudes of 4.3 +/- 0.9 ng/mL (14 +/- 3 nmol/L). The frequency and duration characteristics of the progesterone and LH peaks were not significantly different, but progesterone fractional peak amplitudes were one quarter those of LH pulses. 3) Fractional progesterone peak amplitudes in the seven women correlated inversely (r = -0.811) with 24-h mean LH concentrations, suggesting a negative feedback relationship between progesterone and LH release. 4) LH and progesterone interpulse intervals both exhibited significant nyctohemeral variations, with diurnal amplitudes of 73 +/- 12 min for LH and 43 +/- 8.9 min for progesterone (P less than 0.01). 5) Significant positive cross-correlations existed in all seven women between serum LH and progesterone concentrations considered simultaneously and at progesterone time lags of 10-50 min. By autoregressive modeling, the later (20-50 min) cross-correlations could be accounted for by sustained autocorrelations in the individual progesterone and LH time series and significant cross-correlations between LH and simultaneous progesterone concentrations and between LH and 10-min lagged progesterone concentrations. We conclude that progesterone release occurs in a periodic (circadian and ultradian) fashion as well as in a discrete (episodic or pulsatile) mode. Moreover, both positive and negative feedback relationships operate to coordinate LH and progesterone secretion in the midluteal phase of the human menstrual cycle.     

Pernicious anemia in Latin Americans is not a disease of the elderly

Pernicious anemia is widely regarded as a disease of the elderly. However, it is expressed differently in black women, among the most striking differences being their younger age at presentation of the disease compared with whites. We now compared 92 Latin-American patients with 115 white and 100 black patients to see if similar age differences occur in other racial groups. Latin-American men and women were both significantly younger than white men and women, and were similar in age to blacks. Only 21% of Latin-American patients were 70 years of age or older, compared with 49% of whites. It is apparent that pernicious anemia is indeed predominantly a disease of the elderly in whites but that this is not the case in other racial groups.     

Perceptual responses in patients with inflammatory and functional bowel disease

BACKGROUND AND AIMS: Enhanced visceral sensitivity following a transient inflammatory process in the gut has been postulated as an aetiological mechanism of irritable bowel syndrome (IBS). In this study we compared perceptual responses to rectosigmoid distension in patients with mild chronic inflammation of the rectum (ulcerative colitis (UC)) and patients without mucosal inflammation (IBS) to determine if chronic low grade mucosal inflammation may be a plausible explanation for rectosigmoid hypersensitivity reported in both IBS and UC patients. METHODS: UC disease activity was quantified using activity index scores. Perception thresholds for discomfort during rectosigmoid distension were compared between 11 UC patients with quiescent or mild disease activity, 18 IBS patients, and 13 healthy controls. RESULTS: Although UC activity index scores negatively correlated with perceptual thresholds for discomfort (r=-0.76, p=0.016), UC patients had higher discomfort thresholds compared with IBS patients and controls before (p=0.02) and after (p<0.001) a noxious sigmoid conditioning stimulus. CONCLUSIONS: Rectal perception was attenuated in UC but enhanced in IBS. In chronic mild inflammation, activation of antinociceptive mechanisms may prevent the development of visceral hyperalgesia. Low grade mucosal inflammation alone is unlikely to be responsible for symptoms in functional gastrointestinal disorders.