Germinoma with granulomatous reaction arising from the corona radiata; case report and review of articles]

We report a rare case of germinoma with granulomatous reaction arising from the corona radiata. This 20-year-old man was admitted to our hospital complaining of progressive motor weakness on the right side. CT demonstrated a poorly demarcated high density area in the left corona radiata, which was heterogeneously enhanced after administration of contrast medium. Moreover, the continuity of the mass to the ventricular wall was confirmed on MRI. At the first operation, subtotal removal of the tumor was performed through a fronto-parietal craniotomy. The diagnosis for the specific neoplasm was not established histologically, but granuloma caused by fungal infection was the most likely cause of the lesion. We tried amphotericin B (AmB), and remission of the tumor was obtained. However, during the following 3 months, the size of the tumor gradually enlarged again. AmB was repeatedly administered, but this time the treatment was ineffective. Six months later, on May 21, 1990, the second operation was performed and histological examination revealed typical germinoma consisting of two-cell pattern. Subsequently, the patient underwent focal irradiation of 33 Gy to the tumor site, and the tumor completely disappeared. As intracranial germinomas are observed to be successfully cured by radiotherapy and/or chemotherapy, choice of the therapeutic management must be carefully determined according to the histological diagnosis, especially in young people. A variety of locations of germinomas and the accompanying granulomatous reactions could create some diagnostic confusion, so great care must be taken in the treatment of much intracranial germinomas.     

Independent association of antibodies against human papillomavirus type 16 and E7 proteins with cervical cancer

The E4 open reading frame (ORF) of human papillomaviruses (HPVs) is transcribed in abundant mRNAs encoding an fusion gene during the productive infection, and the HPV 16 E7 ORF encodes an oncoprotein detectable in the cell lines derived from cervical carcinoma. We examined 421 human sera, which included 108 samples from the patients with cervical carcinoma, for the presence of IgG antibodies against the HPV 16 E4 and E7 proteins by enzyme-linked immunosorbent assay. Bacterially expressed fusion protein lac- and nonfusion protein E7 were purified and used as antigens. All of the 22 serum samples positive for anti-E7 antibody and the 11 out of 15 samples positive for anti- antibody were from the patients with cervical carcinoma, but only one sample was found to contain both anti- and anti-E7 antibodies. These findings show specific and independent association of these antibodies with cervical carcinoma.     

Fibrate for treatment of primary biliary cirrhosis

Recent studies of the effectiveness of ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cirrhosis (PBC) reported that UDCA therapy did not necessarily stop the progression of liver fibrosis in all patients, even those with early stage PBC. Thus, there is a need for more effective treatments that could prevent asymptomatic PBC from progressing to the icteric stage. Bezafibrate is effective in approximately two-thirds of non-icteric patients who have not shown a complete response to UDCA. Serum bilirubin, aspartate aminotransferase and γ-guanosine 5'-triphosphate levelswere significantly lower in patients who responded to additional bezafibrate on univariate analysis. The putative mechanism by which bezafibrate acts in cholestasis is by increasing phospholipid output into bile, which forms micelles with the hydrophobic bile acid that reduces its toxicity.     

Surgical treatment for the recurrence of colorectal cancer

We report the results of a retrospective study conducted on patients who developed recurrence following surgery for colorectal cancer, and present a practical plan to improve the survival rates. Of 974 patients who underwent surgery for colorectal cancer in our hospital during the 20 years between 1974 and 1993, 152 developed recurrence, as local recurrence in 70 (7.2%), as liver metastasis in 47 (4.8%), and as pulmonary metastasis in 35 (3.6%). The number of patients who underwent reoperation or curative resection was 54 (77.1%) and 13 (24.1%), respectively, of those with local recurrence, 16 (34.0%) and 6 (37.5%) of those with liver metastasis, and 6 (17.1%) and 6 (100.0%) of those with pulmonary metastasis. The 3- and 5-year survival rates were 13.4% and 8.9%, respectively, after reoperation for local recurrence, 14.4% and 0%, after reoperation for liver metastasis, and 53.3% and 53.3% after reoperation for pulmonary metastasis. Although evaluation was difficult owing to the small number of patients with lung metastasis, resection of a pulmonary lesion resulted in a good outcome. Furthermore, a significant difference in 3- and 5-year survival rates was observed between patients who underwent reoperation and those who underwent conservative treatment, for whom the survival rates were 0% and 0% following local recurrence, 4.6% and 0% following liver metastasis, and 0% and 0% following lung metastasis, at 3 and 5 years, respectively. These findings indicate that aggressive surgery for recurrence may result in a better outcome.     

Characterization of adenosine deaminase (ADA)-negative B-lymphoblastoid cells cocultured with ADA-positive fibroblasts

Abstract: A cell line, BAD05, derived from B lymphocytes of an adenosine deaminase (ADA; EC 3,5,4,4)-deficient patient could not proliferate in a serum-free medium containing 100 μmol/l deoxyadenosine. When BAD05 was cultured with ADA-positive fibroblasts, the proliferation of BAD05 was improved. BAD05 cell density increased when the initially mixed ratio of fibroblasts/BAD05 was 1/10 or higher, but decreased when the ratio was 1/20 or lower. Deoxyadenosine concentrations in the medium and ATP and deoxyATP (dATP) levels in the BAD05 were measured after 4 hours of coculture at initial BAD05 cell densities of 1 × 10⁵and 1 × 10⁶cells/ml. Deoxyadenosine concentrations in the medium decreased as the density of fibroblasts increased. The dATP level decreased as the mixed ratio rose. The ratio of fibroblasts/BAD05 rather than the cell density of fibroblasts had a larger effect on the dATP levels in BAD05. Under our experimental conditions, ADA-negative cells proliferated well when the ratio of ADA-positive cells/ADA-negative cells was over 1/10.     

Molecular design of hybrid tumour necrosis factor alpha with polyethylene glycol increases its anti-tumour potency.

This study was conducted to increase the anti-tumour potency and reduce the toxic side-effects of tumour necrosis factor alpha (TNF-alpha). Natural human TNF-alpha was chemically conjugated with monomethoxy polyethylene glycol (PEG) using succinimidyl coupling of lysine amino groups of TNF-alpha. The number-average molecular weight of PEG-modified TNF-alpha (PEG-TNF-alpha) increased with an increase in the reaction time and the initial molar ratio of PEG relative to TNF-alpha. The resulting modified TNF-alpha was separated into fractions of various molecular weights. The specific activity of separated PEG-TNF-alpha s relative to that of native TNF-alpha gradually decreased with an increase in the degree of PEG modification, but the plasma half-life was drastically increased with the increase in molecular weight of modified TNF-alpha. PEG-TNF-alpha s, in which 29% and 56% of lysine residues were coupled to PEG, had anti-tumour activity approximately 4 and 100 times greater than unmodified TNF-alpha in the murine Meth-A fibrosarcoma model. Extensive PEG modification did not increase its in vivo activity. A high dose of unmodified TNF-alpha induced toxic side-effects, but these were not observed with the modified TNF-alpha s. Optimal PEG modification of TNF-alpha markedly increased its bioavailability and may facilitate its potential anti-tumour therapeutic use.     

Muscle spasm induced sympathetic reflex bursts on microneurography in a case with pontine demyelination

Microneurography was performed in a 39-year-old woman with demyelination of the pontine white matter associated with muscle spasms in the lower extremities. Single bursts on the microneurogram were observed immediately after cessation of the spasm with no systemic changes in the blood pressure or heart rate. Voluntary tonic flexion of the lower extremities induced similar bursts with small amplitudes. These reflex bursts possessed a characteristic of muscle sympathetic nerve activity, because the latency between the peak of each burst and the prior R-wave on the electrocardiograph was constant. The occurrence of these bursts suggests that a segmental compensatory mechanism in the spinal cord may stabilize the muscle blood flow influenced by muscle contraction.     

Gerstmann-Sträussler syndrome — A variant type: amyloid plaques and Alzheimer's neurofibrillary tangles in cerebral cortex

Summary This report presents a variant of Gerstmann-Sträussler syndrome (GSS). A 53-year-old female had developed slowly progressive dementia and atactic gait since the age of 45. No myoclonic jerks and periodic synchronous discharges were observed throughout the illness. The neuropathological study revealed that many amyloid plaques and widespread Alzheimer's neurofibrillary tangles (NFTs) appeared in the cerebral cortex. Characteristically, the plaques reacted with anti-prion protein and none of them reacted with anti- protein, and they were made of many components, including amyloid cores, macrophages laden with lipid granules and/or degenerated neurites. Neuropil threads were seen mainly in amyloid plaques. Moreover, plaques appeared which were confluent and laminar in arrangement in the fifth and sixth cortical layers and had a close relationship to the neuronal loss. There was no spongiform change in the cerebral cortex or cerebellum. The cerebellum was almost intact except for a few amyloid plaques. Ultrastructurally, some of the plaques simulated kuru plaques and others had many degenerated neurites possessing paired helical filaments and other accumulated organelles. GSS has been proposed to include cases with progressive ataxia, dementia and massive multifocal plaques in the brain with or without cerebral spongiform changes. The case presented here is a very peculiar case of GSS. Recently, similar cases have been reported in some large families, diagnosed as familial Alzheimer's disease. These cases may be a telencephalic form with numerous NFTs of GSS.     

Differential diagnosis of adrenal masses by chemical shift and dynamic gadolinium enhanced MR imaging

Chemical shift MRI is widely used for identifying adenomas, but it is not a perfect method. We determined whether combined dynamic MRI methods can lead to improved diagnostic accuracy. Fifty-seven adrenal masses were examined by chemical shift and dynamic MR imaging using 2 MR systems. The masses included 38 adenomas and 19 non-adenomas. In chemical shift MRI studies, the signal intensity index (SI) was calculated, and the lesions classified into 5 types in the dynamic MRI studies. Of the 38 adenomas studied, 37 had an SI greater than 0. In the dynamic MRI, 34 of 38 adenomas showed a benign pattern (type 1). If the SI for the adenomas in the chemical shift MRI was considered to be greater than 0, the positive predictive value was 0.9, and the negative predictive value was 0.94 and kappa = 0.79. If type 1 was considered to indicate adenomas in the dynamic MRI, the corresponding values were 0.94, 0.81 and kappa = 0.77 respectively. The results obtained when the 2 methods were combined were 1, 0.95 and kappa = 0.96 respectively. The chemical shift MRI was found to be useful for identifying adenomas in most cases. If the adrenal mass had a low SI (0 < SI < 5), dynamic MRI was also found to be helpful for making a differential diagnosis.