Estimation of critical points of branched polymers

The authors' theory of the gel point is applied to the gelation experiments in nonstoichiometric systems of Gordon and Scantlebury. Agreement between the theory and the observations is found to be excellent in every region examined, confirming the mathematical soundness of the theory. The theory is transposed to the site-bond problem. With the aid of a high dimension expansion of the ring distribution function, we derive an analytic expression for the bond percolation threshold. The resultant equation is in good conformity with the site-bond percolation simulation of Stauffer. The present theory is scrutinized over a wide range of dimensions for pure bond percolation; the result shows that the theoretical line abruptly merges with the observed points at d=8, consistent with the Lubensky-Isaacson excluded volume theory which predicts the critical dimension d(c)=8 for sol clusters on lattices.

Identification of 187 single nucleotide polymorphisms (SNPs) among 41 candidate genes for ischemic heart disease in the Japanese population.

To investigate whether common variants in the human genetic background are associated with pathogenesis of ischemic heart diseases, we systematically surveyed 41 possible candidate genes for single-nucleotide polymorphisms (SNPs) by directly sequencing 96 independent alleles at each locus, derived from 48 unrelated Japanese patients with myocardial infarction, including 25.8 kb 5' flanking regions, 56.8 kb exonic and 35.4 kb intronic sequences, and 1.8 kb 3' flanking regions. In this genomic DNA of nearly 120 kb, we identified 187 SNPs: 55 in 5' flanking regions, seven in 5' untranslated regions (UTRs), 52 in coding elements, 64 in introns, eight in 3' UTRs, and one in a 3' flanking region. Among the 52 coding SNPs, 26 were non-synonymous changes. Allelic frequencies of some of the polymorphisms were significantly different from those reported in European populations. For example, the Q506R substitution in the coagulation factor V gene, the so-called "Leiden mutation", has a reported frequency of 2.3% in Europeans, but we detected the Leiden mutation in none of the Japanese genomes that we investigated. The allelic frequencies of the -33A>G SNP in the thrombomodulin gene were also very different; this allele occurred at a 12% frequency in the Japanese patients that we examined, although it had been detected in none of 82 Caucasians reported previously. These data support the hypothesis that some SNPs are specific to particular ethnic groups.

Identification of 142 single nucleotide polymorphisms in 41 candidate genes for rheumatoid arthritis in the Japanese population.

Single-nucleotide polymorphisms (SNPs) can make an important contribution to our understanding of genetic backgrounds that may influence medical conditions and ethnic diversity. We undertook a systematic survey of genomic DNA for SNPs located not only in coding sequences but also in non-coding regions (e.g., introns and 5' flanking regions) of selected genes. Using DNA samples from 48 Japanese patients with rheumatoid arthritis (RA) as templates, we surveyed 41 genes that represent candidates for RA, screening a total of 104 kb of DNA (30 kb of coding sequences and 74 kb of non-coding DNA). Within this 104 kb of genomic sequences we identified 163 polymorphisms (1 per 638 bases on average), of which 142 were single-nucleotide substitutions and the remainder, insertions or deletions. Of the coding SNPs, 52% were non-synonymous substitutions, and non-conservative amino acid changes were observed in a quarter of those. Sixty-nine polymorphisms showed high frequencies for minor alleles (more than 15%) and 20 revealed low frequencies (<5%). Our results indicated a greater average distance between SNPs than others have reported, but this disparity may reflect the type of genes surveyed and/or the relative ethnic homogeneity of our test population.

Age invariant of Gompertz function and exponential decay of populations commensuration with CLOV experiments.

The exponential decay law of populations is further examined on the basis of new observations of Japanese and Swedish cohorts. It is shown that the populations decrease exponentially at higher ages in accordance with the theoretical prediction, which confirms the previous conclusion. The theory is applied to recent experiments on Mediterranean fruit flies by Carey et al., (1992, Science, 258, 457-460), the results showing that the exponential decay law holds in sufficient approximation. All the evidences accumulated so far suggest that the decay law is a general theorem. On the basis of this information, we derive a general expression that estimates the limit age as a function of population. The predicted curve is in excellent agreement with the observed limit ages in Japan.

Radiosurgery for arteriovenous malformations with gamma-knife: a multivariate analysis of factors influencing the complete obliteration rate.

Seventy-two patients with arteriovenous malformations (AVMs) were treated with gamma-knife and subsequently analyzed to determine what factors influenced the obliteration of AVMs. The volume of nidi ranged from 0.3 to 21.7 ml (mean 3.9 ml) and the marginal dose ranged from 9 to 31.5 Gy (mean 21.4 Gy). The cumulative obliteration rates of all cases were 41% at 2 years, 67% at 3 years, and 89% at 4 years. Multivariate analysis demonstrated that only the two variables of flow rate (P = 0.020) and dose planning with axial MRI (P = 0.045) had correlation with the obliteration rate. Other variables such as size, marginal dose, and embolization had no statistical correlation with the obliteration rate. It may be very important to evaluate the AVM flow rate to predict the effect of gamma-knife radiosurgery on AVMs, even when the nidi volumes are small.

Quantification of regional cerebral blood flow and vascular reserve in childhood moyamoya disease using [123I]IMP-ARG method.

Both regional cerebral blood flow (rCBF) and regional vascular reserve (rVR) in ten childhood Moyamoya disease were quantified pre- and post-operatively by autoradiographic processing using single photon emission computed tomography (SPECT) and N-isopropyl-rho-iodoamphetamine (IMP) (IMP-ARG method) to estimate hemodynamic effectiveness of surgical revascularization. Before surgery, in two patients, rCBF was reduced in the whole territories and loss of rVR in the anterior circulation was observed; +4.3% in the anterior cerebral artery (ACA), -3.0% in the middle cerebral artery (MCA) and +17.5% in posterior cerebral artery (PCA) territories. After surgery, in eight patients without transient ischemic attack (TIA) episodes, rCBF at rest was maintained around subnormal level in the whole territories, and mean rVR was up to +11.9, +17.3 and +28.3% in ACA, MCA and PCA territories, respectively. However, rVR in the anterior circulation was significantly reduced in comparison with rVR in the posterior circulation. Quantification of both resting rCBF and rVR using IMP-ARG method could provide reliable information concerning on surgical indication and its effectiveness in childhood Moyamoya disease.

Early effects of gamma knife radiosurgery on brain metastases: assessment by 201TlCl SPECT and 99mTc-DTPA-human serum albumin SPECT.

Thallium-201 chloride (201TlCl) single photon emission computed tomography (SPECT) was used to determine tumor viability, and the early and delayed images of technetium-99m-diethylenetriaminepenta-acetic acid-human serum albumin (99mTc-HSA-D) SPECT were used to assess tumor vascularity and permeability, respectively, in 17 patients with 18 brain metastases. SPECT was performed before, 1 week after, and 1 month after radiosurgery. The ratios of 201Tl and 99mTc-HSA-D uptake in a tumor were expressed as a ratio to uptake in the corresponding normal contralateral areas (uptake index). Magnetic resonance imaging with gadolinium was used to determine tumor volume. 201Tl index decreased significantly 1 week (p < 0.05) and 1 month (p < 0.005) after radiosurgery. In contrast, 99mTc-HSA-D indices of early and delayed images obtained at 1 week after radiosurgery were not significantly different from the pretreatment values. However, both were significantly low (p < 0.05) 1 month after radiosurgery. No change in tumor volume was detected 1 week following radiosurgery, but there was a significant decrease (p < 0.005) after 1 month. The reduction in tumor viability that occurs before the appearance of evidence of tumor shrinkage represents the early effect of radiosurgery on brain metastases. Reduction in tumor size, vascularity, and permeability occur subsequently.

[Reliability and factorial structure of a rating scale for persistent vegetative state].

We developed a new rating scale, Kohnan Vegetative Score, to measure severity and small clinical changes in vegetative state patients. It has 7 items corresponding to the conditions of vegetative state by Japanese Society of Neurosurgery: motor function, food ingestion, urination and defecation, eye movement, vocalization, communication, and facial expression. Each item is rated in 5 ordinal categories: slight (score = 1), mild(2), moderate(4), and extreme(5). The sum of the scores is used as the summary score, which ranges from 7 to 35, and high score means 'severe'. We examined the reliability and the factorial structure of the Kohnan Vegetative Score. The subjects were 10 patients who met the conditions of vegetative state. Four neurosurgeons rated the subjects, and then 2 of them repeated the rating after one week interval. As a measure of reliability, the (weighted) Kappa coefficient proposed Cohen (1960, 1968) was calculated for each item, and the intraclass correlation coefficient (ICC) was calculated for the summary score. To analyze the factorial structure, the factor analysis was carried out. The minimum and the maximum weighted Kappa values were 0.44 and 0.64 for intra-rater reliability, and 0.37 and 0.69 for inter-rater reliability, respectively. Concerning the factorial structure, the contribution of the first factor was 91.5% which indicated the unidimensionality of the scale. The ICC's estimate for the summary score were 0.90 (95% C.I.: 0.766-0.970). On the basis of these results, the Kohnan Vegetative Score has unidimensionality and high reliability enough for a practical use.

Multiple segmental agenesis of the cerebral arteries: case report.

A case of multiple segmental agenesis of the cerebral arteries is presented. Cerebral angiography demonstrated bilateral so-called carotid rete mirabile, a similar "rete" of the right vertebral artery and intradural duplication of the left vertebral artery. These abnormalities are thought to be caused by multiple segmental agenesis of the cerebral arteries as they penetrate the dura mater. The embryological and anatomical significance of these findings is discussed.

Effect of gamma knife irradiation on relaxation and contraction responses of the common carotid artery in the rat.

This report concerns a pilot study of the short- and long-term effects of gamma knife radiosurgery on vascular responses. The investigation was carried out on male Sprague-Dawley rats, and the relaxation and contraction responses of the right common carotid artery (CCA) were assessed following irradiation (100 Gy). The non-treated CCA of the same animals served as internal controls. Non-irradiated rats were used to control the effect of normal aging on vascular function. Isometric tension was determined on in vitro preparations of arterial rings. Acetylcholine-mediated, endothelium-dependent relaxation was impaired one month after radiosurgery, as was endothelium-independent relaxation induced by sodium nitroprusside, but the effect on the latter was minimal. The irradiated CCA was also impaired with respect to contraction responses induced by norepinephrine, endothelin-1 or phorbol dibutyrate. This impairment appeared to be biphasic, as it was evident one day after radiosurgery, followed by a partial recovery one week later, and again manifest after one month. At the light microscope level, the carotid arteries appeared to be well preserved throughout the experiment. However, obvious ultrastructural changes were noted in endothelial and smooth muscle cells of specimens obtained three months after radiosurgery. The present data indicate that high dose gamma knife radiosurgery affects the functions of both, the vascular endothelium and the vascular smooth muscles in an apparent time-dependent fashion. Because of its increasing application to patients, there is the need for studying the effects of gamma knife radiosurgery on cerebral arteries, since functional vascular changes may occur in the absence of obvious histological alterations. Our results on CCAs point to the feasibility of such experimental investigations.

Effect of Gamma Knife radiosurgery on acoustic neurinomas. Assessment by 99mTc-DTPA-human serum albumin- and 201TlCl-single photon emission computed tomography.

Single photon emission computed tomography (SPECT) was performed on 16 patients with acoustic neurinoma before and 1 and 2 years after Gamma Knife surgery. 201TICI-SPECT was used to determine tumor viability. Early and delayed images of 99mTc-DTPA-human serum albumin (99mTc-HSA-D)-SPECT were used to assess tumor vascularity and permeability, respectively. There was a statistically significant decrease in the 99mTc-HSA-D index of the early image at 1 year (p = 0.013) and at 2 years (p = 0.018) after Gamma Knife surgery. On the other hand, the 201Tl index and the 99mTc-HSA-D index of the delayed image were not significantly different from their pretreatment values. These observations demonstrate that a reduction in tumor vascularity without a decrease in tumor viability may be one of the effects of Gamma Knife surgery on acoustic neurinomas.

Radiosurgery of brain metastases with the Gamma Knife.

A total of 130 patients with metastatic brain tumors were treated with the Gamma Knife; 85 had multiple lesions. The marginal dose was 14-30 Gy for the initial 20 cases during the first 6 months. Thereafter, we increased the marginal dose to between 25 and 30 Gy for the last 110 cases. The follow-up period ranged from 1 to 49 months (mean 9 months). The recurrence rate fell from 20% for the early low-dose cases to 4.6% for the later 110 higher-dose cases (p = 0.043). Transient neurological deterioration developed in 7 cases (5.4%), and permanent neurological deficits were recognized in a further 6 cases (4.6%). The relatively high prescription dose of 25-30 Gy at the margin of brain metastases treated with the Gamma Knife resulted in an acceptably high control rate with a low rate of complications.

A note on population dynamics.

Population dynamics is analyzed by means of the power series expansion of a decay ratio F(P) with respect to the continuation probability, P, of survival. The truncation of the higher terms of the series yields the Verhulst equation as a first approximation. The approximation for higher age yields a simple exponential decay law of population, while the younger-age approximation recovers Gompertz's empirical law of human mortality. It is shown that there exists a finite survival probability in the limit of t = infinity. The validity of the present result is examined with real population dynamics of centenarians. In order to construct a commensurable definition of aging, an aging phenomenon in decay process is considered on the assumption of an ideal society, from which a simple relationship is derived between the extent of advancement of aging and the continuation probability.

Gamma knife surgery for Cushing's disease.

BACKGROUND: The efficacy of gamma knife surgery on Cushing's disease is not well known to date. In most reported cases of Cushing's disease treated with gamma knife, the area to be irradiated was determined with computed tomography or pneumoencephalography. We report two cases of recurrent pituitary-dependent Cushing's disease treated with gamma knife using stereotactic magnetic resonance imaging (MRI). MATERIALS AND METHODS: Recurrent microadenomas were visualized as hypointense areas using gadolinium-enhanced MRI after two transsphenoidal surgeries in both cases. The doses of irradiation given were 35 Gy and 20 Gy to the margin of the tumors, and less than 8 Gy and 21 Gy to the optic apparatus and cranial nerves in the cavernous sinus, respectively. RESULTS: Both patients had clinical remission with normal serum cortisol and adrenocorticotrophic hormone levels, during 2-year follow-up after radiosurgery, without endocrinologic deficiency or neurologic deterioration. CONCLUSIONS: Gamma knife surgery can be an alternative therapy for Cushing's disease when pituitary adenomas are apart from the optic apparatus and can be visualized clearly by MRI, even if tumors are recurrent after microsurgery.

Gamma Knife surgery for angiographically occult vascular malformations.

To evaluate the effect of radiosurgery on angiographically occult vascular malformations (AOVMs), 9 patients treated with Gamma Knife surgery were followed up for 21-37 months. Eight patients had bleeding episodes, 1 had uncontrollable epilepsy. Rebleeding occurred in 3 AOVMs 5 or 6 months after treatment. One patient experienced transient radiation-induced edema. One patient underwent surgical extirpation due to uncontrollable epilepsy 21 months after Gamma Knife surgery. Histological findings revealed an arteriovenous malformation (AVM) and a cavernous angioma. There was hypertrophy of the internal membrane of the AVM, but no effect on the cavernous malformation. Radiosurgery should only be considered in cases of inoperable AOVM, because there is no definite proof that radiosurgery prevents AOVMs from rebleeding.

[Assessment of vascularity and permeability in brain tumor using SPECT and 99mTc-DTPA-human serum albumin in relation to 201Tl SPECT].

Single photon emission computed tomography (SPECT) using technetium-99m-DTPA-human serum albumin (99mTc-HSA-D) and thallium-201 chloride (201Tl) was simultaneously performed on 25 patients with brain tumors; 10 with brain metastasis, 8 with astrocytoma (Gr. 3) and 7 with meningioma. The early image was obtained 10 minutes after 99mTc-HSA-D (740 MBq) injection, and the delayed image was taken 5 hours after the injection. HSA-D index, based on the ratio of 99mTc-HSA-D uptake in the tumor versus the cortical area, was calculated on each image, and compared with Tl index (tumor/contralateral cerebrum ratio). HSA-D delayed index was significantly greater than HSA-D early index in all tumor types (p < 0.05 by the Wilcoxon ranked sign test). Linear correlation between HSA-D early index and HSA-D delayed index was significant in astrocytoma (Gr. 3) (p < 0.01) and meningioma (p < 0.001), and a linear correlation between HSA-D delayed index and Tl index was significant in astrocytoma (Gr. 3) (p < 0.05). It is concluded that HSA-D early index and delayed index could reflect tumor vascularity and permeability, respectively, and provide supplementary information for Tl index.

Assessment of postischemic reperfusion and diamox activation test in stroke using 99mTc-ECD SPECT.

To evaluate the cerebral distribution of 99mTc-ethyl cysteinate dimer (99mTc-ECD) at blood flow levels beyond the normal range, we investigated postischemic reperfusion and acetazolamide (Diamox) activation test in stroke patients. The postischemic reperfusion was studied in 10 patients who showed a postischemic hyperperfusion area on other single photon emission computed tomography (SPECT) studies using N-isopropyl-rho-[123I]iodoamphetamine ([123I]IMP), 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO), or 133Xe. 99mTc-ECD SPECT demonstrated a hyperactive area in one case, an isoactive area in four, and a hypoactive area in five. Correlations with CT findings revealed hyperactive areas without any abnormality, isoactive areas with perifocal rim, perifocal edema, or diffuse cerebral edema, and hypoactive areas with an infarct core. The Diamox activation test was studied in eight other patients with atherothrombotic stroke, and a limitation in vasodilative capacity was classified into three grades: Gr. 0 (none to minimal), Gr. I (mild), and Gr. II (moderate). [123I]IMP SPECT showed Gr. II and limitation in all eight cases. However, 99mTc-ECD showed Gr. II in three cases and Gr. I in five, and 99mTc-HMPAO revealed Gr. II in two cases, Gr. I in three, and Gr. 0 in three. We suggest that a lack of retention of 99mTc-ECD in a postischemic reperfusion area indicates the severity of the initial brain damage. Although the limitation in vasodilative capacity under Diamox-activated conditions was underestimated using 99mTc-labeled CBF tracers as compared with [123I]IMP, a retention of 99mTc-ECD in the unaffected area with an increased CBF under Diamox activation could be relatively superior to 99mTc-HMPAO.

[A case of cerebral arteriovenous malformation revealed at repeated subcortical hematoma with initially normal angiogram].

An 18-year-old male admitted to our hospital suffered left temporal subcortical hemorrhage. No abnormality was demonstrated on carotid or vertebral angiography at that time. On the day following the onset, left frontotemporal craniotomy was performed and the subcortical hematoma was evacuated. No vascular malformation was found despite careful investigation. On 30th day after the onset, the repeat cerebral angiography was performed but failed to show any vascular abnormalities. After discharge he was in good health, and had had some follow up, CT were normal except for the hematoma cavity. Just two years after the first operation he suffered a second left temporal hemorrhage. Cerebral angiography was repeated and a temporal arteriovenous malformation (AVM) was found with feeding vessels from the M-1 and M-2 portion of the left middle cerebral artery and from the left anterior choroidal artery, and draining veins to vein of Rosenthal and the straight sinus. One month after the second hemorrhage, left frontotemporal craniotomy was performed and complete excision of the AVM was carried out. Only five cases of AVMs in patients with normal angiograms several years before have been reported previously in the literature. But there are no cases in which surgery has been performed. Differently to those cases, in this case it was investigated operatively whether there was a vascular abnormality at the first hemorrhage. We didn't think, however, that the AVM demonstrated at the second hemorrhage had developed spontaneously because there had been a hemorrhage of unknown origin previous to it. It was assumed that a small angiographically occult AVM connected to the hematoma cavity existed at the time of the first hemorrhage but it was too small to be found even during surgical procedure. Such an angiography occult AVM had been growing for two years, and its growth had probably been facilitated by the presence of the hematoma cavity left after the first operation.