Biomedical subjects
Publications and source records attributed to T Iwama.
We report a case of arachnoid cyst in the Sylvian fissure which progressed to uncal herniation. MRI was shown to be superior in visualizing uncal herniation.
A 63 year old female with familial adenomatous polyposis (FAP) complicated by carcinoma of the thyroid and ampulla of Vater and a nonfunctioning adrenocortical adenoma is reported herein. We reviewed 23 cases of duodenal or periampullary carcinoma, 10 cases of thyroid carcinoma and 4 cases of adrenal neoplasm presented in the Japanese literature. From studying these cases, we identified that FAP patients had a high risk of developing periampullary carcinoma and consequently, it is very important to periodically examine the ampulla of Vater. Thyroid carcinomas in patients with FAP were well differentiated carcinomas and occurred earlier than in the general population. The use of medical imaging equipment with mean that insidious abdominal tumors in cases of FAP will be detected more frequently in the future and as patients with FAP have a high risk of developing malignancies, surgery should be indicated for incidentally found adrenal tumors.
Two cases of ulcerative colitis with a positive Coombs test are reported herein. In a 30 year old woman, hemolytic anemia was well controlled by excision of a rectal stump left over from a former operation. A 53 year old woman had a positive Coombs test without clinical hemolytic anemia 10 years after undergoing a total procto-colectomy with ileo-anal anastomosis. Thus we concluded that total procto-colectomy may be preventive, as well as therapeutic, for Coombs positive hemolytic anemia associated with ulcerative colitis.
A case of Crohn's enterocolitis associated with diffuse tracheo-bronchitis is presented herein. Although respiratory tract involvement in Crohn's disease is extremely rare, our review of the world literature revealed several common clinical pathologic features. These features include a productive cough with chest X-ray films which are normal except for some peripheral involvement. Bronchoscopy, however, shows diffuse inflammation of the trachea and bronchi with widely scattered whitish lesions while biopsy reveals a granulomatous infiltration of inflammatory cells. This tracheobronchitis typically responds well to treatment with prednisone.
Postmortem histopathology of eight gliomas was studied in correlation with magnetic resonance imaging (MRI) and computed tomography (CT) findings. MRI demonstrated the lesions more clearly and widely than CT. Also, T2-weighted images (T2WI) had a greater ability to depict the lesion than T1-weighted images (T1WI). The areas in which neoplastic cells had invaded corresponded to the high intensity areas on T2WI in four cases of glioblastoma multiforme. In the case of a grade II astrocytoma, neoplastic cells were scattered beyond the region corresponding to the high intensity area on T2WI. In the case of a grade III astrocytoma, neoplastic cells did not come up to the line corresponding to the margin of the high intensity area on T2WI. In the remaining two cases, although the high intensity areas on T2WI were depicted as being larger than the areas in which neoplastic cells were seen histopathologically, the high intensity regions corresponding to the outside zones of the tumour-infiltrated area were thought to be a radiation necrosis in one case and a 'periventricular high intensity' in the other. The high cellularity of the glioma was seen mainly as a low intensity area on T1WI and as an isointensity or a slightly high intensity area on T2WI. However, the signal intensities of glioma on MRI, reflecting T1 or T2 values of the tumour tissues, did not correlate with the malignancy of the tumour.
Chromosome analyses were performed on benign desmoid tumors obtained from two female patients with familial adenomatous polyposis (FAP), one of whom was diagnosed as having Gardner syndrome (GS). The modal chromosome number was 46 in both specimens, and detailed Q-banding analysis in Case 1 (GS) revealed a clonal abnormality of an interstitial deletion of the long arm of chromosome 5, del(5)(q21q31). The deleted region included an assigned locus for an FAP major gene (5q21-q22). All of the metaphases analyzed in this case showed an extra segment of bright fluorescence on the short arm of chromosome 15, but this unusual chromosome (15p+) was observed in both peripheral lymphocyte and skin fibroblast cultures from the patient, indicating that the 15p+ was constitutional in nature. In Case 2, no clonal rearrangements were identified and most cells had a normal karyotype. However, two cells showed rearrangements involving a 17q with non-identical breakpoints, one of which was observed as a solitary chromosome change. Based on the present findings in Case 1 and those reported so far, the chromosomal defect on 5q might be one of the causal genetic events primarily associated with the development of both benign desmoid tumors and colorectal adenomas and carcinomas in FAP patients.
The effects of the anti-SRS-A agent NZ-107 on antigen-(ovalbumin) and calcium ionophore A23187-induced airway responses in the guinea-pig have been investigated. In the presence of 5 microM indomethacin, NZ-107 (3 microM) did not affect the peak response in ovalbumin-induced contraction but did inhibit the prolonged response following the peak response in the tracheal strip. A higher concentration of NZ-107 (10 microM) completely blocked both peak and prolonged responses. Inhibitory effects of NZ-107 on ovalbumin responses were less in the lung parenchymal strip. The potency of NZ-107 in inhibiting ovalbumin-induced tracheal contraction was not changed in the absence of indomethacin but was reduced in the presence of 45 mM serine-borate, an inhibitor of the conversion of LTC4 to LTD4. NZ-107 inhibited A23187-induced contractions in both tracheal and parenchymal strips but in both cases the inhibitory potency was less than that on ovalbumin response. NZ-107 was a more potent inhibitor of ovalbumin-induced SRS-A release than histamine release in lung fragments but was ineffective in inhibiting A23187-induced SRS-A and histamine release. NZ-107 at a concentration of 10 microM more effectively inhibited LTC4- and histamine-induced tracheal contractions than it did LTC4 in the presence of 45 mM serine-borate. These results suggest that NZ-107 selectively inhibits antigen-induced SRS-A responses in airway tissues of the guinea-pig.
(S)-2-Amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic acid (TAN-950 A (1)) is a novel amino acid antibiotic which shows a high affinity for glutamate receptors of the central nervous system. To improve the affinity for glutamate receptors, the structure-activity relationships of TAN-950 A derivatives 6a--o, 15a--o were investigated. Optically active TAN-950 A analogs 15a--h were synthesized starting with methyl (S)- and (R)-N-Boc-pyroglutamate (8) via acylation at the C-4 position followed by isoxazolone formation with hydroxylamine and subsequent deprotection reactions. The lactam 16, prepared from (RS)-aminoadipic acid, and dimethyl esters 19 of (R)- and (S)-aspartic acid were converted to (RS)-3-methyl-homo-TAN-950 A (15i) and optically active nor-TAN-950 A derivatives 15j--o, respectively, utilizing a similar sequence of reactions. Most of TAN-950 A derivatives 6a--o, 15a--o showed an affinity for glutamate receptors. The 3-alkyl derivatives 15b, d--g, especially, showed a high affinity for the quisqualate subtype-receptor and had a strong activating effect on the hippocampal neurons (glutamate agonistic activity). The (R)-enantiomer 15a of TAN-950 A had increased selectivity for the N-methyl-D-aspartate (NMDA) subtype-receptor. This selectivity was further enhanced by removal of the methylene group in the amino acid moiety of 15a. The most potent and selective NMDA agonistic activity was observed with (R)-3-methyl-nor-TAN-950 A (15m).
We have investigated the effect of NZ-107, an inhibitor of bronchoconstriction induced by slow reacting substance of anaphylaxis (SRS-A), on tracheal responses to adenosine in the guinea pig. In the presence of an adenosine uptake inhibitor, dipyridamole (1 microM), NZ-107 (0.3-1 microM) enhanced adenosine-induced relaxation in 30 nM leukotriene D4 (LTD4)-precontracted trachea, whereas aminophylline (AP, 10-30 microM), an adenosine receptor antagonist, markedly inhibited it. NZ-107 (1 microM) also enhanced the relaxation induced by forskolin, an adenylate cyclase activator, but not that by nitroprusside (NP), a guanylate cyclase activator. AP (30 microM) affected neither forskolin- nor NP-induced relaxation. NZ-107 (1 microM) and AP (30 microM) inhibited to about the same extent the contractile response to an adenosine A1 receptor agonist, the R(-)-enantiomer of N6-(2-phenylisopropyl)-adenosine (R-PIA). The R-PIA-induced contraction was completely blocked by 5 microM indomethacin. NZ-107 (1 microM) did not affect the contraction induced by PGD2, but significantly reduced that of PGF2 alpha. AP (30 microM) had no effect on PGF2 alpha- and PGD2-induced contractions. These results suggest that NZ-107 may have a unique profile for adenosine responses in bronchial asthma.
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Long-term angiographic follow-up was performed 3 years after percutaneous transluminal coronary angioplasty (PTCA) between 1983 and 1986. Among 294 arteries with initially successful dilatation, in which diameter was reduced by more than 20% and residual stenosis was less than 50%, 192 lesions were angiographically patent (50% or less stenosis) in the 6 month follow-up. Three years later, angiography was again performed for 81 lesions. There was no difference between these 81 cases with angiography and the remaining 111 cases in other clinical manifestations except for a higher frequency of diabetes mellitus observed in the angiography group (33% vs 19%). Progressive deterioration of the disease (more than 50% diameter stenosis) was noted in 5 cases, all of which already had relatively severe stenosis (40% or more) in the 6 month follow-up. It was concluded that dilated coronary artery lesions by PTCA can be expected to have good long-term prognosis once they are proven to be patent in the 6 month follow-up angiography.
We conducted these experiments to investigate the differences between continuous portal and one shot portal infusion of 5-fluorouracil (5-FU) using male Donryu rats. Continuous portal infusion of 5-FU (20 mg/kg/day x 5 days) revealed no remarkable side effects on the rats with significant decrease in the number of liver metastases generated by intraportal inoculation of ascites hepatoma AH60C. Consecutive 5-day administration of 5-FU (20 mg/kg x 5) by one shot method via spleen resulted in no metastases but caused death in 75% of rats because of severe leukopenia and dehydration. The rats receiving one shot infusion of 5-FU (33.3 mg/kg x 3, day 1, 3, 5) via spleen showed a significant decrease in the number of metastases without lethal side effects. Continuous portal infusion of 5-FU would be a safe and effective therapy to prevent liver metastases, whereas one shot portal infusion of 5-FU may give rise to severe side effects while preventing liver metastases.
A 64-year-old man was admitted to our department with a diagnosis of rectal carcinoma. Preoperative histological diagnosis was highly differentiated adenocarcinoma of Dukes' A classification (Rb', Is', 20-25 mm in diameter, PM'). Preoperative radiation (2.5 Gray/time, total 30 Gray) and chemotherapy (PSK 3g/day x 3 weeks, ACNU 30 mg/m2/week x 3 weeks) were performed on this lesion. After these therapies, form of the tumor changed to IIa', SM', which was recognized by endo-scopic examination with rectal echography. A reduction of the size was 25%. Low anterior resection, curative operation, was performed 2 weeks after the therapy. The resected rectum was examined in detail, resulting in complete disappearance of the carcinoma cell and the tumor was replaced by the inflammatory cells, fibroblasts and granular cells. These findings were compatible with grade IVB of Ohboshi-Simosatos' classification.
Fusiform aneurysms (FA) and dissecting aneurysms (DA) of the vertebro-basilar systems have been thought to be rare, but recently reports of these aneurysms have increased. The differential diagnosis between FA and DA is requisite for deciding therapy or for prognosis, but it is often difficult to distinguish these aneurysms even if angiographies are conducted. The authors have treated 6 cases with FA and 5 cases with DA during the past 17 years. As the initial symptom, subarachnoid hemorrhage (SAH) was noted in all 6 cases with FA. On the other hand, 2 cases of SAH, 2 cases of brain stem infarction, and 1 case of ischemic attack were noted in DA cases. The aneurysmal locations of FA were at the vertebral artery (VA) in all 6 cases, and those of DA were at the VA in 3 cases and at the basilar artery (BA) in 2 cases. As angiographic findings of DA, pearl & string signs were demonstrated in 3 cases, and retention of contrast medium was noted in 3 cases. Diagnosis of FA is comparatively easy on angiography but when angiospasm exists, it is difficult to differentiate DA from FA. Consequently, repeated angiography is recommended. MR imaging findings of 2 cases with FA were compared with those of 3 cases with DA. No abnormal findings, excepting a dilatation of the signal-void area corresponding to the arterial blood flow were shown in FA, but various abnormalities were detected in all of the 3 cases with DA. Namely, an intimal flap and a double lumen in 1 case, intra-mural hematoma in 1 case, and a hematoma adjacent to the parent artery in 2 cases were demonstrated. Thus, MR imaging was thought to be a useful means for distinguishing between FA and DA.
Loss of heterozygosity (LOH) and K-ras mutation were analyzed in 111 colorectal polyps and 26 invasive carcinomas from 40 patients with familial adenomatous polyposis of distinct histopathological types. LOH, being less than 2% in moderate adenomas, was detected on chromosome 5q (20%) in severe adenomas, on 5q (26%) and 17p (38%) in intramucosal carcinomas, and on 5q (52%), 17p (56%), 18 (46%), and 22q (33%) in invasive carcinomas. LOH on chromosome 5q occurred most frequently in the region close to the APC gene both in adenomas and carcinomas, and a loss of the normal allele of the APC gene was demonstrated in 3 cases. K-ras mutation markedly increased in the step of development from moderate (11%) to severe (36%) adenomas. These results suggest the following mechanisms for the development of colon tumors in patients with familial adenomatous polyposis: (a) the heterozygous mutant/wild-type condition at the APC gene causes formation of mild or moderate adenoma; (b) the loss of the normal allele in the APC gene leads to a change from moderate to severe adenoma; (c) LOH on chromosome 17p contributes to the conversion of adenoma to intramucosal carcinoma; (d) LOH on other chromosomes, such as 18 and 22q, are involved in the progression of intramucosal carcinoma to invasive carcinoma; and (e) K-ras mutation may also affect the development of moderate to severe adenoma.
Ophthalmological examinations were performed in 49 people (43 patients) from 24 families affected by familial adenomatous polyposis (FAP). No features of congenital hypertrophy of the retinal pigmented epithelium (CHRPE) were noted in six first-degree relatives without colonic polyps. Patients with Gardner's syndrome exhibited CHRPE more frequently than those without exostosis or desmoid tumour (91 per cent versus 45 per cent). In addition the prevalence of CHRPE was slightly higher in the patients with gastric or duodenal polyps (68 per cent compared with 50 per cent) in those who had a normal gastroduodenal examination. There were 11 families in which two or more patients underwent ophthalmological examinations. In five of these 11 families, all 12 patients were negative for CHRPE. In four of the remaining six families, all 11 patients had CHRPE. CHRPE is one of the pleiotropy of FAP and ophthalmological examination is an important screening test for the family of patients with CHRPE associated with FAP.
Spin-lattice relaxation times (T1) of water protons and cross-relaxation times (T(IS)) between irradiated protein protons and observed water protons were measured to study water structure in various rat brain tissue. A tumour-bearing rat model and an incomplete forebrain ischaemia model of stroke prone spontaneously hypertensive rats (SHRSP) were used for the experiments. T(IS) and T1 were measured by the inversion recovery FT method with and without f2-irradiation at 7.13 p.p.m. and gamma H2/2 pi approximately 69 Hz, respectively, using a 360 MHz FT-NMR spectrometer. All of experiments on T1 and T(IS) yielded a single kind of component. In spite of small changes in T1 and water content, T(IS) values in peritumoural oedematous and ischaemic brain tissue were significantly shorter than those of normal brain and far shorter than those of brain tumour, indicating a large amount of hydration of marco-molecules in the oedematous and/or ischaemic rat brain tissue. T(IS) might be sensitive parameter for studying the water structure in various brain tissue.
Familial adenomatous polyposis (FAP), which includes familial polyposis coli (FPC) and the Gardner syndrome (GS), is a genetically determined premalignant disease of the colon inherited by a locus (APC) mapping within 5q15-q22. To elucidate the role of 5q loss in FAP tumorigenesis, we analysed 51 colorectal tumors and seven desmoids from 19 cases of FPC and five GS patients, as well as 15 sporadic colon cancers. RFLP analysis revealed a high incidence of allelic deletion in hereditary colon cancers as well as in sporadic colon cancers with a peak at the APC locus. APC loss resulted primarily from interstitial deletion or mitotic recombination. Combined tumor and pedigree analysis in a GS family revealed loss of normal 5q alleles in three tumors, including a desmoid tumor, which suggests the involvement of hemizygosity or homozygosity of the defective APC gene in colon carcinogenesis and, possibly, in extracolonic neoplasms associated with FAP.