Five newly identified HLA alleles: A*0310, A*2907, B*4435, Cw*0206, Cw*0506, and confirmation of A*3106, B*3924, Cw*0314, DRB1*0322, and DRB1*1433 alleles

A number of HLA alleles have been newly identified. This concerns HLA-A*0310, A*2907, B*4435, Cw*0206, Cw*0506, of which Cw*0206 was found in three unrelated individuals, all B*4002 positive. Some other alleles are also presented but confirm earlier detected sequences: A*3106, Cw*0314, DRB1*0322, and DRB1*1433. Moreover, we identified B*3924 in a bone marrow transplant recipient and in five of six unrelated stem cell donors, selected for this patient. In all cases, B*3924 was found on a haplotype combining A*0201, B*3924, Cw*0701, and DRB1*1303. The observation of this extended haplotype is of importance for the selection for stem cell transplantation. Cells expressing B*3924 and B*4435 were typed by serology as B39 and B44, respectively. Cells expressing HLA-A*0310 do not express A3 but type as A-Blank.     

Induction of tyrosine kinase receptor b by retinoic acid allows brain-derived neurotrophic factor-induced amyloid precursor protein gene expression in human SH-SY5Y neuroblastoma cells

Retinoic acid (RA) is a potent regulator of morphogenesis, growth and cell differentiation. Incubation with RA causes arrest of proliferation and neurite extension in SH-SY5Y cells, a neuroblastoma cell line of human origin. In these cells, RA regulates the expression of the β-amyloid precursor protein. The retinoid increases the levels of intracellular and secreted forms of APP (amyloid precursor protein), APP–mRNA levels and the activity of the APP promoter in transient transfection studies. These responses require long periods of exposition to the ligand, thus suggesting a nondirect effect of the RA receptors on the APP gene. Also in these cells, RA induces the expression of TrkB, the tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF), and 4 days of pretreatment with retinoic acid confers BDNF responsiveness to the APP promoter.     

Oxidative stress response involving induction of protective enzymes in Candida dubliniensis.

Candida dubliniensis is a yeast species closely related to Candida albicans, but in contrast to C. albicans, limited information is available on the virulence factors of this important fungal pathogen. The objective of the present study was to determine if this species was able to evoke an adaptive response to oxidants. C. dubliniensis, treated with a low concentration of either H(2)O(2) or methyl viologen (a superoxide generating agent), mounts an adaptive response that results in increased survival against lethal doses of both oxidants. This response was characterized by the induction of enzymes with known antioxidant function. C. dubliniensis strains were less resistant to oxidants than C. albicans, displaying higher susceptibility to their toxic effects. The adaptive response described here might be responsible, among other factors, for the ability of this pathogen to cause infections in individuals with impaired immunity.     

"Low-risk" and "high-risk" HPV-infection and K-ras gene point mutations in human cervical cancer: a study of 31 cases

To analyze the coexistence of human papilloma virus (HPV) infection and K-ras gene activation in cervical neoplasia, we investigated 31 (seven pre-invasive and 24 invasive) cervical carcinomas for "low-risk" (types 6 and 11) and "high-risk" (types 16 and 18) HPVs and K-ras point mutations using PCR-based technology. "Low-risk" HPVs were not detected in the group investigated; however, 20 of 31 (64%) cases were HPV 16 positive, while HPV 18 was found in only three (9.7%) samples (HPV 6/11 v. HPV 16/18, p < 0.0001; HPV 16 v. HPV 18, p < 0.0001; Fisher's exact test). There was a K-ras codon 12 point mutation in two of 31 (6.4%) neoplasms, with none of the cases showing a K-ras codon 13 point mutation. Two moderately differentiated squamous carcinomas showed K-ras exon 2 gene alterations. Interestingly, none of the pre-invasive cervical carcinomas displayed K-ras gene point mutations. The mean patient age did not differ significantly in the number of HPV-positive and -negative cases. A coexistence of "high-risk" human papillomavirus DNA with K-ras gene alterations was observed in three of 31 (9.7%) neoplasms (one IIA and two IB moderately differentiated cervical carcinomas). Our results suggest that "high-risk" HPVs coexist with K-ras gene alterations in a subset of moderately differentiated carcinomas of the cervix uteri.     

High prevalence of tuberculosis in AIDS patients in Spain

A total of 67 cases of tuberculosis was diagnosed in the first 100 cases of AIDS, diagnosed according to the former CDC criteria, at a hospital in Madrid, Spain. This is the highest known prevalence of tuberculosis in AIDS patients both within and outside Spain. The clinical manifestations of tuberculosis were very variable and atypical. The rate of isolation ofMycobacterium tuberculosis from blood was particularly high: of 25 patients in whom blood cultures were performed, 16 were positive. In a third of the patients with proven mycobacteremia, blood was the first or the only positive specimen. In general, therapy resulted in rapid clinical improvement, but in some cases mycobacteria were isolated from clinical or necroscopy specimens months after what was considered adequate therapy.     

Ceroid granulomas in the female genital system.

Three cases of ceroid granulomas of the female genital system are presented, involving the cervix in two and lesions in the ovaries and bowel serosa in the other. Ceroid granulomas are unusual and interesting lesions formed when suitable substrates accumulate within macrophages to such an extent that a relative lack of biological antioxidants results and auto-oxidation and conversion to ceroid is favoured. This may occur in the setting of haemorrhage and necrosis, whether from tumour necrosis or associated with endometriosis. Other sources of lipids and lipoproteins include bile, meconium and vernix caseosa.     

Biochemistry of antral ulcer in patients

Separation and measurement of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenine-adenosine, lipid phosphates (lipid-P), RNA and DNA, furthermore, separation of Mg2+-dependent, total (Mg2+-dependent plus Na+--K+-dependent or Mg2+--Na+--K+-dependent) and Na+--K+-dependent ATPases and measured of their activities were carried out in tissue samples obtained from "ulcerated antral mucosa", from "non-ulcerated antral mucosa" and the muscular layer beneath the examined mucosa specimens, of patients with antral ulcer. It has been found that (1) the tissue levels of ATP, ADP and AMP, of the sum ATP + ADP + AMP, adenine-adenosine, lipid-P, RNA all calculated for 1.0 mg DNA content, further, the activities of Mg2+-dependent, total (Mg2+-dependent plus Na+--K+-dependent) and Na+--K+-dependent ATPase were significantly higher in the ulcerated antral mucosa than those in the control antral mucosa; (2) no significant biochemical alterations were found in the muscles under the ulcerated and non-ulcerated antral mucosa of patients with antral ulcer; (3) the extents of increases in the substrate levels of ulcerated antral mucosa depended on their original levels in the control antral mucosa. The results indicate a cellular hyperfunction in the ulcerated antral mucosa, in comparison with the control one. No circulatory injury could be demonstrated in the ulcerated antral mucosa.     

Measurement of blood loss by total-body counting on the basis of calculated and predicted blood volumes

Blood loss was measured by total-body counting in conformity with the fall in activity, the calculated or predicted blood volumes being known. On the ground of the predicted and calculated blood volumes it was the Nadler formula which gave the best approximation. The method was employed for the measurement of blood loss in users of intrauterine contraceptive spirals. It was found suitable for the measurement of a sudden blood loss of major intensity.     

Suppressive rod-cone interaction in distal vertebrate retina: intracellular records from Xenopus and Necturus

The influence of dim diffuse adapting fields upon the sensitivity to focal photic stimulation was studied by means of intracellular recording in retinal neurons of the south african clawed frog, Xenopus and the mudpuppy, Necturus. In cones and in most horizontal and bipolar cells lacking color opponency, dim diffuse backgrounds have little influence upon the response to diffuse flicker of low (less than 2 Hz) temporal frequencies; however, with small diameter test probes of higher temporal frequencies, presentation of dim backgrounds enhance the peak-to-peak amplitude of responses to sinusoidal flicker by as much as 800%. This background enhancement effect adheres to the spectral sensitivity of the green-absorbing rod photopigment, and appears to be largely independent of the influence of the adapting field upon cone photopigment or ambient membrane potential in the recorded neuron. This effect cannot be obtained with rod-driven flicker responses. We designate this background influence on flicker, suppressive rod-cone interaction (SRCI) and attribute it to a tonic suppressive (probably inhibitory) influence of rods upon cone pathways that is removed by rod light adaptation. SRCI is also observed in the response of most sustained ON and OFF ganglion cells. However, no corresponding effect occurs in rods, color-opponent second-order neurons, ON-OFF amacrine cells, or most ON-OFF ganglion cells. The spatial and temporal limitations of SRCI observed by means of intracellular recording in amphibians are very similar to those documented by means of psychophysical or electroretinogram (ERG) procedures in a wide variety of species including humans (2, 4, 11, 22, 23, 29). SRCI most probably reflects a process that is mediated by horizontal cells. The specifics of the underlying mechanism remain unclear.