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Biomedical subjects

T Okagaki

Publications and source records attributed to T Okagaki.

At least 37 records · Page 2Linked to original sources

The prognostic value of nuclear versus architectural grading in endometrial adenocarcinoma: a Gynecologic Oncology Group study.

The pathologic grade of endometrial adenocarcinoma is widely recognized as an important prognostic and therapeutic indicator. However, disagreement persists about the optimal method of determining grade. The pathology committee of the Gynecologic Oncology Group employs a system based on the proportion of tumor in glandular array; this system is both reproducible and predictive of outcome. Others have suggested that grading based on nuclear pleomorphism and the size of nucleoli provides better prognostication. We compared the three-level architectural grading system (AG) with a two-level nuclear grading system (NG) to determine reproducibility and prognostic value in 88 cases of stage 1 endometrial adenocarcinoma. Three pathologists made independent assessments of grade by each method. The division of tumors by architectural arrangement was superior for predicting survival (83%, 73%, and 44%, AG, p = 0.005; vs. 79% and 61%, NG, p = 0.14) and equivalent to nuclear grading for prediction of recurrence. Both systems were moderately reproducible (k = 0.49, AG; k = 0.57, NG). Assessment of NG was more tedious than that of AG. Subdivision of architectural grade based on high nuclear atypia, as recommended in current, International Federation of Gynecology and Obstetrics guidelines, did not improve prognostication. Because grading based on nuclear pleomorphism does not provide prognostic information superior to that resulting from architectural grading, we do not advocate its use in routine surgical pathology practice.

Adenocarcinoma↗

Renal cell carcinoma extending into left side of double inferior vena cava.

A case of renal cell carcinoma extending into the left side of a double inferior vena cava is presented. En bloc excision of the left inferior vena cava and left kidney was performed without complications. Recognition of various venous anomalies, including double inferior vena cava, is important in the evaluation and surgical treatment of retroperitoneal disease.

Aged↗

The major myosin-binding domain of skeletal muscle MyBP-C (C protein) resides in the COOH-terminal, immunoglobulin C2 motif.

A common feature shared by myosin-binding proteins from a wide variety of species is the presence of a variable number of related internal motifs homologous to either the Ig C2 or the fibronectin (Fn) type III repeats. Despite interest in the potential function of these motifs, no group has clearly demonstrated a function for these sequences in muscle, either intra- or extracellularly. We have completed the nucleotide sequence of the fast type isoform of MyBP-C (C protein) from chicken skeletal muscle. The deduced amino acid sequence reveals seven Ig C2 sets and three Fn type III motifs in MyBP-C. alpha-chymotryptic digestion of purified MyBP-C gives rise to four peptides. NH2-terminal sequencing of these peptides allowed us to map the position of each along the primary structure of the protein. The 28-kD peptide contains the NH2-terminal sequence of MyBP-C, including the first C2 repeat. It is followed by two internal peptides, one of 5 kD containing exclusively spacer sequences between the first and second C2 motifs, and a 95-kD fragment containing five C2 domains and three fibronectin type III motifs. The C-terminal sequence of MyBP-C is present in a 14-kD peptide which contains only the last C2 repeat. We examined the binding properties of these fragments to reconstituted (synthetic) myosin filaments. Only the COOH-terminal 14-kD peptide is capable of binding myosin with high affinity. The NH2-terminal 28-kD fragment has no myosin-binding, while the long internal 100-kD peptide shows very weak binding to myosin. We have expressed and purified the 14-kD peptide in Escherichia coli. The recombinant protein exhibits saturable binding to myosin with an affinity comparable to that of the 14-kD fragment obtained by proteolytic digestion (1/2 max binding at approximately 0.5 microM). These results indicate that the binding to myosin filaments is mainly restricted to the last 102 amino acids of MyBP-C. The remainder of the molecule (1,032 amino acids) could interact with titin, MyBP-H (H protein) or thin filament components. A comparison of the highly conserved Ig C2 domains present at the COOH-terminus of five MyBPs thus far sequenced (human slow and fast MyBP-C, human and chicken MyBP-H, and chicken MyBP-C) was used to identify residues unique to these myosin-binding Ig C2 repeats.

Amino Acid Sequence↗

A novel regulatory effect of myosin light chain kinase from smooth muscle on the ATP-dependent interaction between actin and myosin.

The actin-binding activity of myosin light chain kinase (MLCK) from smooth muscle was studied with special reference to the ATP-dependent interaction between actin and myosin. MLCK in the presence of calmodulin endowed sensitivity to Ca2+ on the movement of actin filaments on phosphorylated myosin from smooth muscle that was fixed on a coverslip. This regulatory effect was not attributable to the kinase activity of MLCK but could be explained by its actin-binding activity. The importance of the actin-binding activity was further substantiated by results of an experiment with Nitellopsis actin-cables in which MLCK regulated the interaction under conditions where MLCK was exclusively associated with the actin-cables.

Actins↗

Regulation by Ca(2+)-calmodulin of the actin-bundling activity of Physarum 210-kDa protein.

From the plasmodia of a lower eukaryote, Physarum polycephalum, we have previously purified a 210-kDa protein that showed similar properties to those of smooth muscle caldesmon. Further characterization of the 210-kDa protein revealed that it bundled actin filaments. This bundling activity was inhibited by calmodulin in the presence of Ca2+. Unlike smooth muscle caldesmon, the 210-kDa protein bundled actin filaments whether or not a reducing agent, such as dithiothreitol, was present. The protein was shown to have two (or more) different actin-binding sites which were classified into salt-sensitive and salt-insensitive sites. Electron microscopy revealed that the 210-kDa protein was an elongated molecule (mean length, 97 +/- 25 nm) which was bent in the middle. The Stokes radius and sedimentation coefficient of the 210-kDa protein were 130 A and 2.9 S, respectively. An immunofluorescence study revealed that the 210-kDa protein colocalized with the bundles of actin filaments in thin-spread preparations of Physarum plasmodia, suggesting that the 210-kDa protein was regulating the appearance and disappearance of the actin bundles that are associated with the contraction-relaxation cycle of the plasmodia.

Actins↗

Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic Oncology Group study.

PURPOSE: The objective of this study was to determine if groin radiation was superior to and less morbid than groin dissection. METHODS AND MATERIALS: Members of the Gynecologic Oncology Group randomized 58 patients with squamous carcinoma of the vulva and nonsuspicious (N0-1) inguinal nodes to receive either groin dissection or groin radiation, each in conjunction with radical vulvectomy. Radiation therapy consisted of a dose of 50 Gray given in daily 200 centiGray fractions to a depth of 3 cm below the anterior skin surface. RESULTS: The study was closed prematurely when interim monitoring revealed an excessive number of groin relapses on the groin radiation regimen. Metastatic involvement of the groin nodes was projected to occur in 24% of patients based on this Group's previous experience. On the groin dissection regimen, there were 5/25 (20.0%) patients with positive groin nodes. These patients received post-operative radiation. There were five groin relapses among the 27 (18.5%) patients on the groin radiation regimen and none on the groin dissection regimen. The groin dissection regimen had significantly better progression-free interval (p = 0.03) and survival (p = 0.04). CONCLUSION: Radiation of the intact groins as given in this study is significantly inferior to groin dissection in patients with squamous carcinoma of the vulva and N0-1 nodes.

Adult↗

Resolution of pulmonary metastases with chemotherapy in a patient with placental site trophoblastic tumor.

Placental site trophoblastic tumor (PSTT), a rare variant of gestational trophoblastic disease, was first described in 1976. PSTT is usually seen in young women, generally treated by hysterectomy, and is associated with a 20% fatality rate. The development of metastases secondary to PSTT is associated with an extremely poor prognosis. Metastatic PSTT has generally been resistant to chemotherapy although one complete and some partial responses have been noted previously. We report a case of a complete chemotherapeutic response in a patient with pulmonary metastases.

Journal Article↗

Ultrastructure of the guinea pig pancreas in acute hypercalcemia.

The effect of acute hypercalcemia on pancreatic ultrastructure and the ultrastructural localization of calcium during hypercalcemia were studied in the guinea pig pancreas. After 3 h of i.v. calcium infusion (0.6 mmol/kg/h), hypertrophy and distention of the Golgi apparatus and an increased number of condensing vacuoles were seen. At 6 h, vacuolar fusion and displacement of zymogen granules occurred. At 9 h, irregular distribution of zymogen granules, indentation of the nucleus with chromatin clumping, and inclusion of intact cell organelles were present. Disruption of the plasma membrane and release of cell organelles into the interstitial space were seen. Control animals receiving saline solution (0.9% NaCl) revealed normal pancreatic ultrastructure. The serum ionized calcium values were 0.65 +/- 0.36 mM in controls and 0.71 +/- 0.14, 0.79 +/- 0.21, and 1.22 +/- 0.50 mM at 3, 6, and 9 h of calcium infusion, respectively. The ultrastructural localization of calcium was performed with the pyroantimonate staining technique after 3 h of calcium and saline infusion. Large calcium deposits were found in calcium-treated animals along the plasma membrane and in the Golgi region. The findings indicate that calcium exerts a strong stimulatory effect that eventually leads to the degeneration of the pancreatic acinar cell.

Acute Disease↗

Morphologic scales and relative distances between lesions identified on Papanicolaou smears.

We fit a Gaussian-type curve to a nonmonotonic transform of initial arbitrarily given scales (pseudoscalar transform) of a two-way discrete classification table by maximizing the likelihood (entropy) and computing morphologic scales of clusters of objects identified by visual judgments. The scales give the relative distance between pairs of categories or states. Morphologic scales of histologic lesions (states) identified on Papanicolaou smears were computed from a confusion matrix consisting of 3,545 matched pairs of observations on Papanicolaou smears and colposcopically directed biopsies available from the Gynecologic Cytology Laboratory, University of Minnesota, between 1985 and 1987. The original (uncollapsed) confusion matrix consisted of eight cytologic categories and histologic states: normal plus atypical benign, reactive atypia (including condylomatous changes); mild, moderate and severe dysplasia; squamous carcinoma in situ; invasive squamous cell carcinoma; and other malignancies. The morphologic scales are expressed numerically, which reflects a degree of confusion between two diagnostic categories or states. Except for malignancies other than squamous cell carcinoma, morphologic scales of histologic states seen from cytology retained the order of clinical severity. We detected a high degree of confusion between severe dysplasia and carcinoma in situ. Malignancies other than squamous cell carcinoma fell between moderate and severe dysplasia. Such a transposition of the scales in this group containing adenocarcinoma was likely due to frequent association of adenocarcinoma with cervical intraepithelial neoplasia. Morphologic scales of cytologic categories seen from histology showed high degrees of confusion and transpositions between mild and moderate dysplasia and between severe dysplasia and carcinoma in situ.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Information, discrimination and divergence in cytology. V. General symmetry of total discrimination and total divergence.

Total discrimination and divergence are derived from Baye's theorem and based on backward (a posteriori) probabilities. Total forward (a priori) discrimination and divergence can be computed from a test matrix from which total backward discrimination and divergence were calculated for optimization of the classifications of gynecologic cytology (Papanicolaou smears) and quality control in a laboratory. The total forward discrimination and divergence appears to behave in parallel with the total backward discrimination and divergence, and the discrepancies in the backward and forward discrimination/divergence were the smallest near the optimum classification scheme. Conversely, the discrepancies between backward and forward discrimination and divergence may be helpful in finding the best classification scheme for gynecologic cytology. The general symmetries of the total backward and forward discrimination/divergence may be related to the human cognitive process of preferring symmetry and to the historic process in which cytologic classification followed histologic classification and continuously checked for matches in two directions--i.e., from histology to cytology and vice versa--thus resulting in the preservation of symmetry.

Bayes Theorem↗

Information, discrimination and divergence in cytology. VI. Biases and errors of measurement in small samples.

Total discrimination and total divergence have been shown to be useful measures of performance in diagnostic cytology. The sample size, Ns (observed number of cytology-histology pairs, essential components of a confusion matrix), may be small for the comparison of two or more laboratories or periodic quality control using observed values. From actual data from previous reports in this series, the best estimation of the confusion matrix of a population was obtained by fitting a Gaussian-type curve after pseudoscalar transform of ranks (row and column numbers). Small sample confusion matrices were generated by Monte Carlo simulation to 2.5 x 10(-7) resolution. To keep measurement biases within +/- 0.5 decits, we found that 100-200 samples of cytology-histology pairs were required in the best classifications of three, four and five category-states. At these sample sizes, measurement errors (standard errors) were also contained within +/- 0.5 decits. This study also confirmed that previously reported overestimated propagated errors in small samples were in fact overestimation and that their use for testing a null hypothesis was valid. The number of samples with indefinable statistics due to a zero denominator can be as high as 30% when the sample sizes are 500 for three, four and five category-state classifications. Biases due to small samples were positive for most category-states except for the optimum three category-states, in which bias changed to negative ("bias inversion"), and observed errors of discrimination and divergence paradoxically decreased as Ns decreased ("error-sample paradox") for a small sample size (Ns less than 700).(ABSTRACT TRUNCATED AT 250 WORDS)

Cytodiagnosis↗