Differentiation of human bone marrow cells into T lymphocytes by in vitro incubation with thymic extracts

Extracts of human or calf thymus influence differentiation of human bone marrow cells in vitro. Incubation of a putative stem cell fraction of human marrow with extracts of thymus for a period of 2 hr led to the appearance of lymphocytes with surface antigens recognized by a highly specific anti-T-cell antiserum. To a lesser degree, development of lymphocytes having the capacity to form rosettes with sheep erythrocytes was observed. Treatment of the so-called stem cell fraction with thymic extracts did not yield cells responsive to mitogenic influences of phyto-haemagglutinin or allogeneic cells. This model should permit further analyses of immunodeficiency diseases and provide a useful technique for purification and analysis of thymus extracts active with human haematopoietic cells.     

The changing epidemiology of hepatitis A in children and the consideration of active immunization in Korea

Currently, Korea is a low endemicity country for HAV, especially in children. However, recent reports of hepatitis A outbreaks show that there has been a shift of disease incidence to adolescents and young adults, with 2 cases of acute liver failure in one reported outbreak. We need to study the immune status for HAV in order to provide information for the establishment of preventive measures and possible consequences of HAV in Korea. A total of 334 infants, children and adolescents less than 20 years of age living in rural areas of Kyonggi Province, Korea were evaluated for anti-HAV immune status in 1996. Five hundred and eighty-four primary school children living in the same area were separately evaluated for the natural seroconversion rate between 1993 and follow-up samples taken in 1996. Anti-HAV IgG antibody was measured by enzyme immunoassay (HAVAB EIA kit, Abbott Laboratories, Chicago, Illinois, USA). In comparison with previous reports of seroprevalence rates, our data confirmed a dramatic drop in seroprevalence rates among children and adolescents under 20 years of age living in rural areas, from over 63.8% two decades ago to 4.6% in 1996. Natural acquisition of HAV antibody in primary school children rarely occurs, registering only 0.5% during three years. Several outbreaks in young adults during 1996-1998 suggested that immunity against HAV in this population is so low that massive outbreaks are unavoidable. Teenagers and young adults, especially soldiers, who are likely to be exposed to contaminated food or water, would also have a greater risk of hepatitis A. Immunizing children with HAV vaccine as a routine schedule should also be considered in Korea in the future, particularly if the disease burden could be estimated and the cost-effectiveness of the vaccine could be proved.     

A 5-year retrospective analysis of alpha-interferon usage

Alpha interferon is an immune modulator used in the treatment of hematologic malignancies and immunosuppressive diseases. While many of the clinical indications for interferon have been well described and are FDA-approved, a large number of clinical uses of interferon are being developed. This study evaluated the appropriateness, efficacy, and safety of interferon therapy at our institution from 1987 to 1991. Data were collected by chart review. Response rates of patients in this hospital were compared to those published in the literature. Twenty-six patients were prescribed alpha interferon. Ten patients (38%) demonstrated a partial response, the highest responses seen in Hairy cell leukemia (67%) and chronic myelogenous leukemia (57%). Response rates for each disease compared favorably to those predicted from the literature. Twelve patients (46%) demonstrated intolerance. Overall five patients (19%) remain on therapy. While interferon appears to be moderately effective in certain diseases, intolerance to interferon seems to be the major limiting factor to its clinical application.     

Age-dependent differences in flurothyl seizure sensitivity in mice treated with a ketogenic diet

Despite strong clinical data confirming the anticonvulsant efficacy of a ketogenic diet (KGD) in pediatric patients, corroborative experimental data in young animals are limited. In the present study, the effects of a KGD on flurothyl seizure susceptibility were examined in normal juvenile mice after a dietary duration of 3, 7, or 12 days, and in adult mice for 15 days. In all groups of KGD-treated mice, blood beta-hydroxybutyrate levels were significantly elevated over those measured in controls. The present KGD was anticonvulsant (i.e. delayed onset) against the first (clonic) flurothyl-induced seizure for juvenile mice treated for either 7 or 12 days, but not for juvenile mice and adult mice fed the diet for 3 and 15 days, respectively. While this KGD was not anticonvulsant against the second (tonic extension) seizure induced by flurothyl in any of the juvenile groups, it significantly delayed tonic extension in the adult group. In addition, juvenile mice fed a KGD exhibited a lower mortality rate following flurothyl-induced seizures compared to mice fed a standard diet. In our discussion of animal models of the KGD, we highlight the need to understand better the impact of important variables such as dietary composition, genetic background, and mode of seizure induction in the study of the KGD.     

Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.     

Lamotrigine-induced tic disorder: report of five pediatric cases

PURPOSE: To describe the clinical spectrum of lamotrigine (LTG)-induced tics (an uncommon side effect) in children. METHODS: Retrospective analysis of patients from our hospital-based practice who developed tics while on LTG. Data obtained from medical records, interviews with parents, video-EEGs, and homemade videotapes. RESULTS: Three males and two females (range, 2.5-12 years; mean, 6.9 years) developed a movement disorder within the first 10 months of therapy (maintenance doses, 4-17 mg/kg/day). Four patients exhibited simple motor tics; one patient experienced mostly vocal (i.e., gasping sounds) tics. Laryngoscopic evaluation of one 2.5-year-old with repetitive gasping sounds was normal. In three cases, tics resolved completely within 1 month of drug cessation; tics recurred in two of these patients after reintroduction of LTG. A fourth patient experienced gradual improvement after stopping LTG over 4 months; the fifth patient's simple motor tics improved spontaneously with a reduction in medication. None of the patients had clinical features of a neurodegenerative disorder, and none met diagnostic criteria for Tourette syndrome. Two patients, however, had a diagnosis of acquired epileptic aphasia syndrome, and one patient had nonprogressive expressive and receptive language dysfunction. A fourth patient had global static encephalopathy, and the fifth patient had only attentional problems. In all patients, tics were not associated with ictal EEG changes. CONCLUSIONS: LTG may infrequently induce simple motor tics, vocal tics, or both. Patients with severe language dysfunction may be particularly susceptible to this uncommon side effect. Further studies are necessary to clarify the population at risk.     

The microbiome of lung cancer tissue and its association with pathological and clinical parameters

Lung cancer is the primary cause of cancer-related deaths worldwide. Recently, although the microbiome has emerged as the key modulator of the carcinogenesis, it has not been evaluated in lung cancer. Here, we evaluated the microbial composition of lung cancer tissues according to the histologic type and genetic mutation, compared it with that of the adjacent normal lung tissues, and investigated the association between the lung microbiome and clinical parameters. We collected lung tissue samples from 162 patients with non-small cell lung cancer (NSCLC, 162 cancer and 54 adjacent normal tissues), surgically resected between January 2018 and December 2019, and analyzed their microbiome using 16S rRNA gene amplicon sequencing, the QIIME2 pipeline, and statistical analyses. NSCLC tissues had significantly lower alpha diversity than the normal tissues, and their microbial composition differed according to the histologic type and cancer genetic mutation. The genera Romboutsia, Novosphingobium, Acinetobacter, and Prevotella were significantly overrepresented in NSCLC tissues. Alpha diversity steadily declined from a normal to a more advanced stage, and microbial compositional differences were noted along with recurrence. Stenotrophomonas was the most predominant genus in the NSCLC tissues of patients with recurrence. The pathways related to the tricarboxylic acid cycle and L-glutamate and L-glutamine biosynthesis were predominant in adenocarcinoma, whereas those related to purine and pyrimidine nucleotide degradation and formaldehyde assimilation were predominant in squamous cell carcinoma. Our findings suggest that the altered lung cancer microbial composition might be associated with cancer initiation and/or progression.