Multiple cerebral infarctions after atypical herpes simplex encephalitis.
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Biomedical subjects
Publications and source records attributed to S M Yamada.
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Gliomatosis cerebri is considered grade III astrocytoma because of the short survival period of patients with this tumor, while the tumor histologically consists of widespread low grade astrocytoma cells. The authors tried to clarify this discrepancy by applying genetic analysis of the tumor. A 29-year-old man originally presented with mild headache and showed diffuse high intensity areas in both hemispheres and in the cerebellum by T2-weighted magnetic resonance imaging (MRI) without gadolinium-dimeglumine (Gd)-enhancement in T1-weighted imaging. Histological diagnosis was gliomatosis cerebri with diffuse grade II astrocytoma. Seven months after temporary improvement following irradiation and chemotherapy, he developed progressive mental deterioration, and died in one year after the surgery. At this time T1-weighted imaging showed Gd-enhanced lesions with enlargement only of the cerebellar tumor. Genetic analysis demonstrated positive FGFR 1 and less FGFR 2 mRNA in the tumor tissue, and FGFR 1 mRNA was beta type dominant. These results indicated that the genetic features of this tumor are similar to those of glioblastoma multiforme concerning FGFR expression. The authors conclude that genetic investigation of the tumor tissue is required to predict the prognosis of gliomatosis cerebri patients, in addition to imaging and histological examinations.
Hemangioblastomas are benign vascular tumors that often occur in the cerebellum, and are located near the pia mater. The blood supply is usually received through the pia mater, and rarely through the external carotid artery. The present cases of hemangioblastoma received blood supply from the external carotid artery (occipital artery) and a branch of the internal carotid artery (carotico-tympanic artery or artery of Bernasconi Cassinari) through the dural branches. The dural arteries were not the main feeders in either case, but preoperative embolization of the occipital artery contributed to minimum bleeding during the operation in one case. Incomplete resection of hemangioblastoma is related to multicentricity of the tumors, small mural nodules, or brain stem involvement. Angiography is valuable for demonstrating arterial supply to small or multiple mural nodules. Conventional angiography is necessary for investigation of the external carotid artery branches.
Astrocytes exhibit significant changes in fibroblast growth factor receptor (FGFR) gene expression during malignant progression. These changes include induction of FGFR1 and concomitant loss of FGFR2 expression. The induction of FGFR1 is believed to endow malignant astrocytes with a selective growth advantage. Glioblastoma (the most malignant form of astrocytoma) cell lines, which exhibit the same pattern of FGFR gene expression as glioblastoma biopsies, were used to evaluate the contribution of FGFR1 expression to glioblastoma cell growth. Addition of phosphorothioate-modified antisense oligonucleotides complementary to the initiation site or the alpha exon of the FGFR1 gene suppressed growth of human glioblastoma-derived cell lines. Reverse antisense controls or antisense oligonucleotide complementary to FGFR2 had no effect on proliferation. Consistent with its growth-suppressive effect, FGFR1 antisense oligonucleotides markedly reduced expression of both FGFR1 mRNA and high-affinity bFGF binding sites, whereas FGFR1 reverse antisense control oligonucleotide had no effect. Antisense oligonucleotide targeted to the alpha exon of the FGFR1 gene suppressed alpha and beta alternatively spliced FGFR1 mRNA isoforms but did not alter the expression of related FGFR family members. Fluorescein-labeled antisense and reverse control oligonucleotides demonstrated cellular uptake and nuclear accumulation. These results indicate that alterations in FGFR expression may contribute to malignant proliferation in human astrocytomas. These findings also illustrate the high degree of selectivity that can be obtained with antisense oligonucleotides, a property that is essential for employing these reagents therapeutically.
With the ultimate goal of minimizing exposures, we conducted a hazard analysis on bloodborne disease transmission at our hospital to identify appropriate control interventions. We utilized basic principles of occupational epidemiology to gather information on the severity and extent of exposures. Because we suspected inadequate reporting of needlestick injuries, we collected 339 reported exposures of health care workers; we conducted a survey of all workers requiring universal precautions training for bloodborne pathogens. The annual incidence of exposures reported was 93.7 per 1000 workers who required this training. Sharps accounted for 83.5 percent of these exposures. Exposure sources demonstrated 4.3 percent positive for HIV, 4.4 percent positive for hepatitis B, and 7.1 percent positive for hepatitis C. The survey indicated that blood/body fluid exposures were underreported by at least fourfold. House officers were most at risk. At-risk behaviors were identified by the significant differences in knowledge of HIV transmission and work practices between groups reporting no or single exposures versus groups reporting multiple exposures. Increased emphasis should be placed on education, reporting exposures, and training house officers in procedures requiring the use of hollow bore needles. This study shows how the use of occupational epidemiology principles and methods were utilized in conducting a thorough hazard analysis and in identifying appropriate control methods.
Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are not commonly recognized in healthy patients without predisposing risk. We performed a retrospective study of patients hospitalized with community-acquired MRSA infections from 1992 to 1996 in Honolulu to determine if community-acquired MRSA infections occurred in patients without known risk. Patients hospitalized within the previous 6 months or transferred from other hospitals or nursing homes were excluded. Epidemiological and clinical data were obtained from an inpatient chart review. Ten (71%) of 14 patients with community-acquired MRSA infection had no discernible characteristics of MRSA infections. Thirteen (93%) patients had skin or soft-tissue infections and one patient had MRSA pneumonia. Isolates from patients with MRSA infection were more likely to be susceptible to ciprofloxacin (P = .05), clindamycin (P = .03), and erythromycin (P = .01) than were those from MRSA-colonized patients. In our population, the majority of community-acquired MRSA infections occurred in previously healthy individuals without characteristics suggestive of MRSA transmission.
Although normal human astrocytes rarely express fibroblast growth factor receptor 1 (FGFR 1) mRNA, expression of FGFR 1 mRNA in astrocytomas increases as malignancy progresses. This result suggests that FGFR 1 can be one of important factors for glioblastoma cell growth. In our study, specific antisense oligonucleotides for FGFR 1 mRNA inhibited cell growth of SNB 19, human glioblastoma cell line, while sense oligonucleotides showed no cell reduction. And Southern blot analysis demonstrated decreased expression of FGFR 1 mRNA in only antisense group. Furthermore, cross-linking analysis revealed decreased number of FGFR 1 in antisense-treated SNB 19 in protein level. These results conclude that cell growth inhibition was caused by suppression of both transcription and translation of FGFR 1 mRNA. Interestingly, alpha-specific antisense also inhibited expression of beta-, and gamma-type of FGFR 1 mRNA which had no binding sites for the oligonucleotides. This fact indicates that antisense oligonucleotides binds to premature mRNA, which is previous form of mature mRNA before splicing, in nucleus. It is previously reported that basic fibroblast growth factor (bFGF), major ligand to FGFR 1, was overly expressed in human malignant astrocytomas. Thus, increased number of FGFR 1 may contribute to the acceleration of bFGF autocrine or paracrine mechanism in glioblastoma.
Although fibroblast growth factor receptor (FGFR) 4 has been reported not to be expressed in normal human astrocytes, we have demonstrated expression of FGFR-1, -3, and -4 in six human glioblastoma cell lines (SNB19, T98G, UW18, D54 MG, U251MG, and U373MG) by RT-PCR Southern blot analysis. All six lines exhibited predominantly beta-type (with only two extracellular Ig-like domains) FGFR-1 expression. In contrast, FGFR-2 expression was only detected in the UW18 cell line. This evidence support our previous observation that malignant progression in astrocytomas is associated with a shift in FGFR-1 mRNA splicing from the alpha-type (with three extracellular Ig-like domains) to the beta-type with concomitant loss of FGFR-2 expression. It also demonstrates the unique finding that FGFR-4 induction in astrocytomas is associated with transformation. In addition to these cell lines, expression of FGFRs was analyzed in normal human brain tissue and in human astrocytoma tissue samples corresponding to different grades of malignancy. FGFR-4 mRNA was undetectable in normal adult white matter, the site of origin of astrocytomas, while astrocytomas of all grades exhibited significant expression of FGFR-4 mRNA as determined by RT-PCR Southern blot analysis. The proportion of FGFR-4 mRNA did not appear to change in relation to the malignant progression of the astrocytomas. This suggests that induction of FGFR-4 expression in astrocytes represents an early event in their malignant transformation. Induction of FGFR-4 in malignant astrocytomas is consistent with previous reports demonstrating that expression of aFGF, which activates FGFR-4, increases in astrocytomas. The simultaneous induction of FGFR-4 and aFGF may establish a potential autocrine pathway that endows astrocytoma cells with a selective growth advantage. Interestingly, very high expression of FGFR-4 mRNA was found in human fetal brain tissue. The above findings suggest that the malignant transformation of astrocytes may involve the activation of a fetal growth promoting pathway.
Penicillin remains the drug of choice for the treatment of streptococcal pharyngitis, with erythromycin as an alternative drug for individuals who cannot take penicillin. Two areas of concern in the management of streptococcal pharyngitis are (1) the prevalence of penicillin-tolerant group A beta-hemolytic streptococci reported in recent studies and (2) the high prevalence of erythromycin resistance in some geographic areas. We tested 305 isolates of group A beta-hemolytic streptococci from Hawaii and the Philippines for penicillin minimum inhibitory concentrations and minimum bactericidal concentrations and erythromycin minimum inhibitory concentrations. There was no evidence of penicillin resistance or tolerance. The prevalence of erythromycin-resistant and moderately susceptible isolates was 3.6% and 2.3%, respectively. There was a trend toward greater erythromycin resistance levels among Hawaiian isolates, but this was not statistically significant.
The Culturette Brand rapid latex agglutination test was compared with the throat culture for accuracy in detecting Group A beta-hemolytic streptococci (GABHS) on paired throat swabs from 1047 children with suspected streptococcal pharyngitis. In this comparison the rapid latex agglutination test had a sensitivity of 78%, a specificity of 88%, a positive predictive value of 52% and a negative predictive value of 96%. In 45 study patients from whom it was possible to obtain paired acute and convalescent sera, the latex agglutination test and the throat culture were compared against each other for detection of infection due to GABHS as evidenced by a 4-fold or greater titer rise of serum antistreptococcal antibodies. The latex agglutination test detected and failed to detect the same number of infections as the throat culture. Thus although a significant number of false positive latex agglutination tests occurred when compared to the throat culture, there is limited evidence in this study that the latex agglutination test is equal to the throat culture in detecting patients who have serologically confirmed infection due to GABHS.