X-linked lymphoproliferative syndrome: abnormal antibody responses to bacteriophage phi X 174.
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Biomedical subjects
Publications and source records attributed to K Sakamoto.
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The effect of trapidil on experimental hyperlipemia and atherosclerosis induced by 1% cholesterol diet in SPF male rabbits (JW/KBL) was investigated by the determination of the lipid contents of the plasma and thoracic aorta and examination of morphological changes in the aorta. Trapidil inhibited the increase of total lipid (TL), total cholesterol (TC), free cholesterol (FC) and phospholipid (PL) by the cholesterol diet in all groups. The level of cholesterol (HDL-C) and phospholipid (HDL-PL) in high density lipoprotein (HDL) remained unchanged after the cholesterol diet and trapidil administration. The atherogenic index (TC-HDL-C/HDL-C, PL-HDL-PL/HDL-PL) was improved by the inhibition of TC and PL by the administration of trapidil. A morphological study of the aorta showed that trapidil inhibited lipid deposition. A microscopic observation of the intima by Sudan III stain showed that inhibition of lipid deposition corresponded with the quantity of trapidil administration. An observation of aorta using transmission electron microscopy (TEM) showed that trapidil inhibited the presence of form cells due to HCD. This inhibition corresponded with the quantity of trapidil administration; and no form cells were seen in the 50 mg/kg-administered group. An observation of intima using scanning electron microscopy (SEM) showed that trapidil inhibited the irregularly elevated regions by HCD. The structure of intima in the 50 mg/kg-administered group was similar to that of the control groups. The observation of the head angiogram showed that trapidil improved the stenosis in the lingual and temporal arteries which was caused by HCD.
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During the course of a review of our patients with bullous pemphigoid (BP), we found that one of our patients had a nephew with the disease. This report presents the cases and suggests that genetic factors may play a role in the pathogenesis of BP. To our knowledge, the occurrence of BP among relatives has not been recorded in the literature.
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Ochotona rufescens is an animal species native to Afghanistan, and is among many new animal species currently being raised for use in experimental research in Japan. In the present paper, we report morphological findings on ocular and auditory character of Ochotona rufescens examined first under normal conditions and then under the influence of various agents, and the results were compared with those on other experimental animals used in this study. On histological examination, the cochlear portion of the labyrinth was found to consist of a coiled canal making two and one half turns from its basal end to the upper turn, and was identical to those of cats and rabbits. Moreover, triple rows of outer sensory hair cells and a single row of inner sensory hair cells were observed. Kanamycin and furosemide (Lasix), a diuretic, were administered 10 min. apart to determine the effects of these drugs on pinna reflex, however, as a result of these administration, none of the Ochotona rufescens tested showed any appreciable depression of this reflex. By funduscopic observation with photographic records, principal retinal arteries were hardly demonstrable except for extremely vague chorioidal vessels, in the layer of the pigmented epithelium which had a puce-like color. Ay contrast, retinal veins were seen in the fundus oculi, as well as whitish optic nerves. The amplitude of the "a" wave in the electroretinogram (ERG) of Ochotona rufescens was only 1/6 that of albino rats or albino rabbits, but the "b" wave was similar in amplitude for all these three species.(ABSTRACT TRUNCATED AT 250 WORDS)
Recent advances in cancer radiotherapy have been remarkable and this is mainly due to the contribution of radiation physics and progression of radiation physics and progression of techniques for irradiation. However, it seems to be needed of tumor radiobiological contribution to obtain better results of cancer radiotherapy in future. In present paper co-operative study between fundamental research and clinical work in radiation oncology is discussed by reviewing co-operation of fundamental research and clinical trial in hyperbaric oxygen radiotherapy in England.
MCNU is a new derivative of nitrosourea and experimental studies have shown equal or superior activity to known nitrosourea compounds. Twenty one cases were entered into our clinical studies with a phase II study. Nineteen cases have had a several courses of prior chemotherapy. Four out of 21 cases achieved a partial response (each one of lymphoepithelioma, parotid gland cancer, recurrent uterine cancer and recurrent breast cancer). The major toxicity encountered during treatment was myelosuppression. Full recovery of myelosuppression was delayed and was seen six to eight weeks after each injections. These initial results justify further clinical investigations with MCNU.
Recently, there has been an increasing interest in the diagnostic and prognostic usefulness of tumor-associated antigen of embryonic and fetal origin. Many approaches have been attempted to make an early diagnosis of the pancreatic cancer, where a specific screening blood test for the pancreatic cancer is required. By using antiserum to fetal pancreas, Banwo et al, discovered an oncofetal antigen that was present in human fetal pancreas, pancreatic tumor tissue, and sera from patients with the pancreatic cancer. Pancreatic oncofetal antigen (POA) was considered to be an oncofetal antigen for human pancreas, and its measurement seemed to be useful in the diagnosis of pancreatic cancer. But elevated levels of POA were also observed in the serum of some patients with cancer of the stomach, lung, colon, or liver as well as in the serum of some pregnant women and others with certain benign conditions. In summary, combined assay with various tumor markers was considered to be useful for the diagnosis of pancreatic cancer.
Two pediatric patients with life-threatening Epstein-Barr virus infections were studied immunologically and treated with acyclovir [9-(2-hydroxyethoxymethyl) guanine]. The patient with chronic active Epstein-Barr virus infection who experienced massive hepatosplenomegaly, pancytopenia, and failure to thrive demonstrated abnormalities of T and B lymphocytes. A second patient, with the X-linked lymphoproliferative syndrome, experienced a rapidly fatal course of acute Epstein-Barr virus infection which typifies this yet undefined immunodeficiency to Epstein-Barr virus. In each case, objective evidence for clinical improvement or antiviral effect of acyclovir treatment was not apparent. Abnormally productive Epstein-Barr virus infections did not appear to play a major role in the clinical syndromes observed. Current studies are focused on treatment of immunologically normal patients with early complicated Epstein-Barr virus infection.
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Hepatocellular carcinoma (HCC) associated with cirrhosis and HCC developing in a noncirrhotic liver may have differing pathogeneses. To study this possibility, 425 autopsied cases of HCC were investigated. Of these, 45 livers were not cirrhotic, 50 were highly cirrhotic (liver weight less than 99 g), and the remaining 331 were cirrhotic but not so highly. The average age was significantly older in the highly cirrhotic group, suggesting a longer premalignant period of chronic liver disease. The liver weight in the noncirrhotic group was about 3.5 times that in the highly cirrhotic group. Hepatitis B surface antigen was positive in serum in only 9.3% and in liver tissue in 10% in the noncirrhotic cases, the positivity rate being much lower compared with other groups (P less than 0.005--0.01), yet antibody to HB core was positive in 90%. The antibody titers were low, however, indicating that these noncirrhotic patients had in the past had HB virus (HBV) infection with no residual chronic B hepatitis. Analysis of the grades of anaplasia of cancer tissue demonstrated an inverse correlation between the degree of fibrosis and grade of anaplasia, i.e., the more advanced the fibrosis, the less anaplastic the cancer. These data suggest that HCC arising in highly cirrhotic liver and in noncirrhotic livers have different pathogenetic backgrounds, and that HBV infection, even though transient, has a certain role in hepatocarcinogenesis. The generally held conjecture that HCC in a noncirrhotic liver is caused by nonviral carcinogens and HCC arising on the ground of cirrhosis is due to HBV seems untenable in such a simple concept.
Analyses of 100 subjects with the X-linked lymphoproliferative syndrome (XLP) in 25 kindreds revealed four major interrelated phenotypes: infectious mononucleosis, malignant B-cell lymphoma, aplastic anemia, and hypogammaglobulinemia. Eighty-one of the patients died. Two male subjects were asymptomatic but showed immunodeficiency to Epstein-Barr virus (EBV). Seventy-five subjects had the infectious mononucleosis phenotype and concurrently, 17 subjects of this group had aplastic anemia. All subjects with aplastic anemia died within a week. Aplastic anemia did not accompany hypogammaglobulinemia or malignant lymphoma phenotypes. Hypogammaglobulinemia had been detected before infectious mononucleosis in three subjects, after infectious mononucleosis in five subjects, and was not associated with infectious mononucleosis in 11 boys with hypogammaglobulinemia. In nine subjects infectious mononucleosis appeared to have evolved into malignant lymphoma; however, the majority of patients with malignant lymphoma showed no obvious antecedent infectious mononucleosis. One subject had infectious mononucleosis following recurrent malignant lymphoma. Twenty-six of 35 lymphomas were in the terminal ileum. Results of immunologic and virologic studies of 15 survivors revealed combined variable immunodeficiency and deficient antibody responses to EBV-specific antigens. Mothers of boys with XLP exhibited abnormally elevated titers of antibodies of EBV. Subjects of both sexes with phenotypes of XLP should be investigated for immunodeficiency to EBV. Persons with inherited or acquired immunodeficiency may be vulnerable to life-threatening EBV-induced diseases.
The frequencies of chromosomal aberrations and sister chromatid exchange (SCE) were measured in lymphoblastoid cell lines (LCLs) and in phytohemagglutinin (PHA)- and pokeweed mitogen (PWM)-stimulated lymphocytes from males with X-linked lymphoproliferative (XLP) syndrome, their obligate carrier mothers, and control subjects. We observed an increased frequency of chromosomal aberrations including increased polyploidy in LCLs derived from families with XLP with time in culture. The SCE rate in LCLs (mean of 3.89 SCEs per cell) was much lower than that in PHA- or PWM-stimulated lymphocytes: PWM-stimulated lymphocytes showed 9.58 SCEs per cell and PHA-stimulated cells had 11.38 SCEs per cell. A greater number of chromosomal gaps and breaks in the D-group chromosomes of LCLs of affected males and carrier females were identified compared to the number expected, based on chromosomal length and the number of aberrations seen in PHA-stimulated cell cultures. No differences in the frequency of SCEs or chromosomal aberrations were found in control subjects and affected males or carrier females in the peripheral lymphocytes stimulated by PHA. Phenotypes of XLP appear to arise from failure of immune responses to Epstein-Barr virus (EBV) and not from intrinsic chromosomal breakage or instability.
In normal pregnant women, reactivation of Epstein-Barr virus (EBV) frequently occurs. Cellular immune responses are apparently suppressed, but high titer EBV-specific antibodies of IgG class may compensate. The antibodies cross the placenta and protect the infant against primary infection for many months. Reactivation of EBV in pregnancy and oral excretion of virus by normal pregnant women could be one explanation why young children in large sibships (among families of low social classes) become infected early in life. Infants are likely infected by EBV from their pregnant mothers who shed virus in saliva. Moreover, the natural protection for several months in the perinatal period against Burkitt lymphoma and fatal EBV-induced lymphoproliferative diseases in congenitally immune deficient children is explained. The maturity and immunocompetence of the immune system at the time of primary infection by EBV and the size of the sibship seem to determine whether infectious mononucleosis occurs. Gammaglobulin derived from human cord blood may be a valuable source of viral-specific antibodies for serotherapy in immune deficient patients.