A NOVEL DRB1*0801 HAPLOTYPE CARRYING DRB3*0202 FOUND IN A GERMAN PEDIGREE

DRB1*08 haplotypes have not been known to carry a DRB3 gene. We have found a patient suffering from liver disease who has a novel HLA haplotype of DRB1*0801 with DRB3*0202 as established by family segregation. These two genes were confirmed by sequencing. DR8 and DR52 antigen specificities were serologically detected, indicating expression of these genes.     

Proliferative response of T lymphocytes to a proline-rich polypeptide (PRP): PRP mimics mitogenic activity of Il-1

Mitogenic properties of a proline-rich polypeptide were investigated. The mitogenic action of PRP was compared with the mitogenic action of Il-1. PRP was not mitogenic for thymocytes at doses 0.01-50 micrograms/ml. PRP, at doses 0.1-50 micrograms/ml, augmented the proliferative response of thymocytes to Con A in a similar fashion as Il-1. At doses higher than 10 micrograms/ml, PRP induced proliferation of lymph node cells and splenocytes as well as T cells from the lymph nodes. It did not, however, cause significant proliferation of B cells from the lymph nodes, at the doses used. PRP did not induce proliferation of an antigen specific Lyt 1+ T cell clone. Il-1 behaved in a similar way as PRP in all the tests described. We consider a possibility that under physiological conditions, at a very early stage of postneonatal life, PRP may replace some functions of Il-1.     

Chromosome changes associated with spontaneous phenotypic variation of transplantable melanoma

The chromosome constitutions of black-melanotic (Ma), brown-melanotic (MI), and amelanotic (Ab) melanomas of the Syrian hamster were compared. The MI and Ab melanomas arose through a spontaneous phenotypic alteration of the Ma tumor. All three variants differ in their growth rates, with MI showing the slowest, Ab the fastest, and Ma intermediate growth rate. Cytogenetic examination revealed that each tumor line shows a distinct karyotype. The Ma tumor is near-diploid, whereas, Ab and MI tumors are hypertriploid and near-tetraploid, respectively. Each tumor line shows a unique set of marker chromosomes, though some markers are shared by two different tumor lines. No single marker chromosome was common for all three melanoma variants. We conclude that the spontaneous phenotypic variation of transplantable hamster melanomas is associated with profound changes in the chromosome constitution of the neoplastic cells. The general direction of these changes is toward increased ploidy and increased complexity of the structural abnormalities.     

2-Mercapto-ethanol enhancement of agglutination reaction--a possible in vitro serological correlate for assessment of functional immunity in simian malaria

Conventional indirect haemagglutination test was performed in rhesus monkey sera (collected from Plasmodium knowlesi infected animals) with and without prior treatment of sera with 2-mercapto-ethanol (2-ME). Surprisingly, many sera samples showed significant enhancement of final titre with 2-ME. The 2-ME enhancement effect was more pronounced in the sera of hyperimmune monkeys on further injection of antigen or parasites. It was also noticeable in the sera during primary drug-suppressed P. knowlesi infection and appeared to have a bearing on the immune status of the animals to rechallenge. The use of a soluble antigen prepared from P. knowlesi infected erythrocytes was found to be essential in IHA test to demonstrate the 2-ME enhancement effect. Antigen prepared from freed parasites (commonly used) failed to show a similar effect in IHA. The possible role of certain T-lymphocyte products - antigen binding, non-agglutinating, 2-ME sensitive molecules - in malarial immunology has been proposed.     

Morphological features of nerve terminal degeneration as part of the remodeling process in the motor endplate in adult muscles

With the exception of signs of retraction and withdrawal, there have been few morphological data concerning degenerated neural profiles in adult motor endplates. Here, investigation into the ultrastructure of the soleus motor endplates of adult rats (4 months old) turned up particular axonal degeneration in approximately 3% of the subjects. These axons occur as synaptic debris in the synaptic matrix of the motor endplate, adjacent to thin processes of the perisynaptic cells occupying the outer most layer of the motor endplate and were devoid of basal lamina. They often possessed dense-cored vesicles (50-80 nm). Axonal debris released from Schwann cell processes occurred during the period of acute sciatic neurectomy, when nerve terminals progressively disrupted within the motor endplate associated Schwann cells. Finally, immunohistochemical staining for antibodies to label macrophages (ED1 or ED2) has shown that nerve fiber-associated macrophages are located near the motor endplate. The results suggest that during the course of endplate remodeling, a few parts of the terminal branches are disposed of through spontaneous collapse, subsequent release from the Schwann cell investment, and eventual ingestion by macrophages in the perisynaptic space.     

Apoptosis of malignant cells in Hodgkin's disease is related to expression of the cdk inhibitor p27KIP1

Previous results from B-cell chronic lymphocytic leukaemia suggest that expression of p27KIP1 might be important in protection from apoptosis. Given the relevance of apoptosis to the pathogenesis of Hodgkin's disease (HD), it was decided to examine the expression of p27KIP1 in relation to apoptosis in these lesions. Paraffin-wax sections from a total of 65 histologically confirmed HD tumours were used to derive apoptotic index (AI) and DNA fragmentation index (DFI) scores, which were compared with the expression of various cell-cycle-regulating proteins, including p27KIP1 (p27), p21WAF1/CIP1 (p21) and cyclin D1, and with Epstein-Barr virus (EBV) status. The DFI was measured by TdT-mediated dUTP-FITC nick end-labelling (TUNEL), and the AI by conventional morphology. Cells showing the typical morphology of apoptosis, together with those resembling so-called 'mummified' Hodgkin/Reed-Sternberg (HRS) cells, were included in AI measurements. Increasing numbers of p27-positive HRS cells were associated with lower levels of apoptosis in these cells, as indicated by significantly lower AI and DFI scores. There was a trend towards poorer survival in those patients with the highest numbers of p27-positive HRS cells and with lower AI and DFI scores, but these differences were not statistically significant. p21-positive HRS cells were significantly more frequent in those cases with lower AI scores. A similar trend was observed for p21 and DFI, although this relationship was not statistically significant. There was also a trend towards higher levels of cyclin D1 protein in HD cases with high AI and DFI values. A tendency for increasing numbers of p27-positive and p21-positive HRS cells in EBV-positive cases was noted, but this relationship was not statistically significant. EBV status did not correlate with either AI or DFI scores. The results of this study suggest that p27, and possibly also p21, may be involved in protection from apoptosis in HD.     

Developmental delays associated with prenatal alcohol exposure are reversed by thyroid hormone treatment

Exposure to alcohol in utero has been associated with hypothyroidism and a variety of developmental defects characteristic of thyroid dysfunction. The present work examined whether these abnormalities could be reversed in infant rats treated with thyroid hormones. Subjects were offspring of dams which were on the following diet regimen during gestation: (1) free access to liquid diet containing ethanol (alcohol pups); (2) an equal volume of isocaloric liquid diet (pair-fed pups); or (3) ad libitum control diet (control pups). Neonates from each group were foster-nursed by control dams, and received triiodothyronine (T3; 0.1 mg/kg/day; s.c.) or saline treatments on postnatal days 1 to 10. The alcohol neonates displayed reduced serum thyroxine which was restored to normal by postnatal day 14. In addition, these pups showed a delayed appearance of developmental landmarks, including righting reflex, dental eruption, auditory startle response and eye opening. The retarded incisor eruption and eye opening were reversed in alcohol pups by T3 treatments. The present data suggest that at least some of the developmental abnormalities associated with prenatal alcohol exposure are attributable to perinatal hypothyroidism and can be restored by early hormone replacement therapy.     

Testicular regression in a patient with virilized female phenotype

The 16-year old girl studied here had ambiguous external genitalia, ie, enlarged clitoris, pseudo vagina, and rudiments of Wolffian tubes. Her karyotype was 46,XY and she was H-Y antigen-positive. In spite of absence of gonadal tissue, genital virilization suggests presence of testes during embryogenesis. This patient is compared to 20 others with testicular regression from the literature. Autosomal-recessive inheritance of this condition is proposed.