Comparison of the Antiemetic Effect of Aprepitant/granisetron and Palonosetron Combined with Dexamethasone in Gynecological Cancer Patients Treated with Paclitaxel and Carboplatin Combination Regimen.

A triple antiemetic therapy combining aprepitant (APR) with conventional double antiemetic therapy, including 5-hydroxytryptamine 3 receptor antagonist (5-HT3-RA) and dexamethasone (DEX), is recommended for preventing chemotherapy-induced nausea and vomiting induced by a carboplatin (CBDCA) regimen. However, consensus on the additive effects of APR for gynecological patients on a combined regimen of paclitaxel and CBDCA (TC regimen) has yet to be reached. This retrospective study investigated the antiemetic effects of palonosetron and DEX (PD therapy) and granisetron and DEX with APR (GDA therapy) in patients with gynecologic cancer and who underwent their first TC regimen cycle between April 2017 and March 2020 at the Gunma University Hospital Outpatient Chemotherapy Center. The results showed that the complete response rate of the 92 patients who underwent PD therapy (PD group) and the 46 patients who underwent GDA therapy (GDA group) were both 80.4% (p = 1.000), and the complete control rates of the PD and GDA groups were 78.3% and 80.4%, respectively (p = 0.828), resulting in no significant difference. Furthermore, we observed no significant difference between the PD and GDA groups in the incidence of grade ≥2 nausea, vomiting, and anorexia (nausea: 7.6% vs. 0%, p = 0.095; vomiting: 4.3% vs. 0%, p = 0.301; and anorexia: 9.8% vs. 2.2%, p = 0.164). Concerning adverse events, compared to the PD group, the GDA group showed significantly higher incidence of grade ≥2 malaise (7.6% vs. 19.6%, p = 0.039). Given the lack of difference in the antiemetic effects of PD and GDA therapies, antiemetic therapy should be selected carefully for individual patients by accounting for the incidence of adverse reactions and interactions with APR.

Acute methemoglobinemia associated with ochronotic valvular heart disease: report of a case.

We describe the first reported case of acute methemoglobinemia associated with ochronotic valvular heart disease. A 79-year-old man with ochronotic valvular heart disease experienced decreased urinary output starting 9 days after an operation. Thereafter, the patient's methemoglobin concentration acutely increased, indicating systemic cyanosis, while the arterial partial oxygen pressure (PaO (2)) was maintained at around 200 mmHg. In patients with ochronotic valvular heart disease, acute methemoglobinemia may occur, as in cases of renal failure or oliguresis.

Novel gene sequences expressed by human melanoma cells identified by molecular subtraction.

Despite the variety of approaches used, only a limited number of tumor-associated antigens have been described for each histological type of tumor. In this report, we present a new strategy involving molecular subtraction to identify novel melanoma-associated gene sequences. Toward this end, 156 complementary DNA clones were isolated with a subtracted melanoma complementary DNA probe (melanoma minus lung carcinoma) after screening 2 x 10(4) independent recombinants of a melanoma expression library by in situ plaque hybridization. These clones were then polymerase chain reaction amplified, screened for duplication, and categorized into 53 discrete genes. By applying poissonian distribution to the numbers of duplicate isolates, we found most of the genes to be rare messages, present at less than 1 copy/200 molecules of mRNA in a typical somatic cell. Messages specific for a type of tissue are usually expressed in this range. The expression of the 53 genes was further studied in human tumor cell lines and normal tissues. Partial sequence data obtained for 20 complementary DNA clones revealed 8 novel human genes. The mRNA transcripts for 5 of the novel genes were identified by Northern blot analysis. Thus, molecular subtraction appears to be applicable for the identification of novel tumor-associated sequences. Some of the potential advantages and limitations of this technology are discussed, including its application to the molecular characterization of immunogenic melanoma-associated antigens.

Parathyroid hormone increases the number of tartrate-resistant acid phosphatase-positive cells through prostaglandin E2 synthesis in adherent cell culture of neonatal rat bones.

Tartrate-resistant acid phosphatase (TRAP) is expressed during one of the steps of osteoclast differentiation. The involvement of prostaglandin E2 (PGE2) synthesis in PTH-induced increases in TRAP-positive cell number was studied in an improved slowly adhering cell culture system, prepared by removing preexisting osteoclasts from disaggregated bone cells obtained from 6-day-old rats. The majority of the TRAP-positive cells that appeared were mononuclear. In 1-day culture, PTH (0.025-0.25 nM) and PGE2 (1 microM) increased the number of mono- and multinucleated TRAP-positive cells. Indomethacin (50 microM) inhibited PTH-induced increase, and the inhibition was significantly abolished by the addition of PGE2. SC-19220, a specific antagonist for one class of PGE2 receptor, inhibited the increase induced by PTH and PGE2. PTH significantly stimulated the production of PGE2 in the culture. Peroxides, which are produced as byproducts of PGE2 biosynthesis, were detected in the adherent cells using dichlorofluorescene and increased the number of TRAP-positive cells. Small resorption pits were recognized on the surfaces of bone slices on which slowly adhering cells had been incubated for 3 days with PTH. These findings showed that PTH, through its effects on PGE2 synthesis and the subsequent reactions, induced the step at which TRAP is expressed, possibly during the differentiation of osteoclasts.

Effect of surface roughness on proliferation and alkaline phosphatase expression of rat calvarial cells cultured on polystyrene.

Rough-surfaced substrates made by a variety of methods have been shown to influence osteoblast proliferation and differentiation. The purpose of this study is to confirm the role of surface roughness in promoting osteoblastic differentiation using tissue culture polystyrene as substrate, by excluding factors other than roughness. Immature osteogenic cells derived from fetal rat calvariae were cultured on the plastic cover strips having varied degrees of roughness created by treatment with four kinds of grinding paper of different particle sizes. The proliferation and gene expression of alkaline phosphatase (ALP) and osteocalcin of the calvarial cells increased on the rough-surfaced cover strips. These levels increased in response to the increase in the degree of surface roughness up to 0.8 microm of average roughness and then decreased to the level observed for the smooth surface. These results demonstrate that the surface roughness itself caused increases in osteoblastic proliferation and differentiation in cell cultures.

Performance on motor tasks as an indication of increased behavioral asymmetry with advancing age.

Age-related asymmetrical functional decline was tested on a sample of 64 right-handed volunteers between 60 and 64 years of age who were free from neurological illnesses and physical handicaps. Increase in functional asymmetry was explored by examining performance indexes for each hand and superiority of the dominant hand on motor tasks of different complexities: the Finger Tapping Test, the Grooved Pegboard Test, and the Pin Test. Our study revealed an increase in superiority of the right hand with age on a highly demanding task (Pin Test). This finding is discussed in light of the hypothesis of a decline in callosal functioning with age and the alternative hypothesis of a greater vulnerability of the right hemisphere in the elderly.

SC-19220, a prostaglandin E2 antagonist, inhibits osteoclast formation by 1,25-dihydroxyvitamin D3 in cell cultures.

1,25 Dihydroxy vitamin D3 (1,25(OH)2D3), prostaglandin (PG) E2 and parathyroid hormone (PTH) induce osteoclast formation in cell cultures. Previously, we have shown that SC-19220, an antagonist of the EP1 subtype of PGE receptors, inhibited tartrate-resistant acid phosphatase (TRAP)-positive cell formation by PGE2 and PTH in adherent cell cultures taken from neonatal rats. Since 1,25(OH)2D3 has been shown to induce osteoclast formation through PGE2 synthesis, in this study we have examined the effect of SC-19220 on osteoclast formation induced by 1,25(OH)2D3 in cell cultures by measuring bone resorption as well as TRAP-positive cell formation. SC-19220 inhibited osteoclast formation by 1,25(OH)2D3 as well as by PGE2 in cell cultures. The addition of SC-19220 to the later half but not to the earlier half of the culture inhibited 1,25(OH)2D3-induced formation. In the culture in which hydroxyurea was added in the later half period, SC-19220 inhibited osteoclast formation by 1, 25(OH)2D3. Under these conditions, 17-phenyl PGE1, an EP1 agonist, induced osteoclast formation. Thus, SC-19220 inhibits certain reactions in the later processes of osteoclast formation induced by 1,25(OH)2D3. In addition, SC-19220 also inhibited osteoclast formation induced by interleukin (IL)-11 and IL-6 as well as by PTH. It is suggested that the SC-19220 inhibiting reactions are shared by all the inducers including 1,25(OH)2D3 and are essential for osteoclast formation.

Microsatellite deletion mapping on chromosome 10q and mutation analysis of MMAC1, FAS, and MXI1 in human glioblastoma multiforme.

Glioblastoma multiforme (GBM) is an end-stage brain tumor of glial origin. Allelic deletions encompassing all or part of chromosome 10q occur frequently in GBMs, indicating that loss of one or more tumor suppressor genes on 10q plays a role in GBM formation. One of these genes is MMAC1 (PTEN), a gene on 10q23 which encodes a dual-specificity protein phosphatase. We carried out a loss of heterozygosity (LOH) analysis of 66 GBM patients using microsatellite markers for 27 loci on 10q. Overall, LOH was detected in 70% of cases, most showing LOH with every informative marker. Eleven patients showed partial 10q deletions, the smallest spanning a 35 cM region distal to D10S187. Sequence analysis of the MMAC1 gene in 45 of these tumors revealed mutations in eleven cases (24%), all with LOH on 10q. None of these mutations was present in normal DNA from the same patients. In addition, we utilized SSCP analysis to test two other candidate genes on 10q: FAS, a cell surface receptor which transduces an apoptotic, cell death signal and MXI1, a transcriptional repressor. The absence of mutations in these genes suggested that FAS and MXI1 are not likely to be tumor suppressor genes physiologically relevant to GBM. These data do support a significant role for MMAC1 in GBM.

Subcellular localization and properties of N-acetylglutamate synthase in rat small intestinal mucosa.

N-Acetylglutamate synthase [EC 2.3.1], which catalyzes the synthesis of N-acetylglutamate, a key effector of carbamoyl-phosphate synthase (ammonia) [EC 6.3.4.16] in the liver of ureotelic animals, was demonstrated to be present in rat small intestinal mucosa. The activity of the enzyme was estimated to be 0.17 nmol N-acetylglutamate formed X (g mucosa)-1 X min-1 at 25 degrees C. Little activity was found in the muscle layer and serosa of the small intestine. The intestinal villous cells were separated from everted intestine, disrupted by nitrogen cavitation, and fractionated into nuclear, mitochondrial, microsomal, and soluble fractions. The mitochondria isolated by this method retained integrity of respiratory function. The mitochondrial fraction was further subjected to isopycnic centrifugation using Percoll (colloidal silica coated with polyvinylpyrrolidone). The activities of N-acetylglutamate synthase and the first two urea cycle enzymes, carbamoylphosphate synthase (ammonia) and ornithine carbamoyltransferase [EC 2.1.3.3], were cofractionated with mitochondrial marker enzymes during the cell fractionation and the isopycnic centrifugation. N-Acetylglutamate synthase, purified 8-fold from the acetone powder extract of small intestinal mucosa, had a high substrate specificity for L-glutamate and acetyl-CoA. The synthase reaction fitted normal Michaelis-Menten kinetics with respect to both L-glutamate (apparent Km, 2.5 mM) and acetyl-CoA (apparent Km, 0.8 mM). L-Arginine stimulated the enzyme activity by increasing the maximal velocity with no effect on apparent Km values for the substrates. These properties were similar to those of the rat liver enzyme (Shigesada & Tatibana (1978) Eur. J. Biochem. 84, 285-291). These results suggest that a function of the intestinal N-acetylglutamate is to activate carbamoyl-phosphate synthase (ammonia) and to allow citrulline synthesis in the tissue.

Immunochemical study of polysaccharide antigen in Streptococcus sobrinus and Streptococcus downei with a cross-reactive monoclonal antibody.

A monoclonal antibody (mAb h-448) was prepared after cell fusion of mouse myeloma cells (SP2/0-Ag-14) to the spleen cells of mice immunised with serotype h strain (MF25) of Streptococcus downei. The antibody (IgM class) reacted in enzyme immunoassay only with whole cells as well as purified polysaccharide (PS) antigen of Streptococcus sobrinus (types d and g) and Streptococcus downei (serotype h), but not with cells or purified PS antigen from any other serotypes of the mutans group of streptococci. mAb h-448 also quantitatively precipitated in solution with the purified antigens. Competitive hapten inhibition tests demonstrated that beta-methylgalactopyranoside inhibited the reaction most strongly. Although rhamnose also showed a substantial inhibitory effect, the results of this study indicate that the antigenic determinant of the PS antigen has a structure similar to the beta-methylgalactopyranoside molecule.

Ornithine carbamoyltransferase deficiency: coexistence of active and inactive forms of enzyme.

Kinetic and molecular properties of liver ornithine carbamoyltransferase from a female patient with the enzyme deficiency were studied. The enzyme activity in the patient was 9% of that in controls. Kinetic properties of the enzyme from the patient appeared to be identical to those of the control enzyme; apparent Km values for L-ornithine and carbamoyl-phosphate at pH 7.2 were 1.3 mmol/l and 7.9 mumol/l, respectively. Patient and control livers contained similar amounts of protein cross-reactive with antibody to the bovine enzyme. No difference in the subunit size was observed between the patient enzyme and the control enzyme. When extracts of control liver were analyzed by isoelectric focusing, a major peak of immunoreactive protein with a pI value of 7.3 and a minor peak with a pI value of 6.8 were observed, and both forms were enzymatically active. On the other hand, extracts of the patient's liver gave a major peak of immunoreactive protein with a pI value of 7.0 and a minor one with a pI of 6.8; the minor form was enzymatically active while the major one showed little or no activity. These results indicate that the patient's liver contained an inactive form of ornithine carbamoyltransferase in addition to an active form of the enzyme, and may reflect the X-linkage of the enzyme at the molecular level.

Differential display of messenger ribonucleic acid: a useful technique for analyzing differential gene expression in human brain tumors.

In this study, a differential display method for messenger ribonucleic acid was successfully used to identify genes differentially expressed between normal human brain and malignant glioma tissues. A total of 60 differentially expressed sequences were initially identified, of which 21 were cloned and sequenced. Twenty of the cloned sequences represented novel genes, and one sequence represented a kinesin heavy chain (KHC) gene isoform. The KHC isoform was selected for further characterization. Northern blots of total ribonucleic acid isolated from normal brain and a glioblastoma were probed with our KHC probe and confirmed the differential expression of this gene. Expression analysis of a variety of normal human tissues demonstrated that this KHC isoform is expressed only in brain tissues, with no detectable expression in placenta, spleen, kidney, lung, liver, or skeletal muscle. Our results confirm the rapid and sensitive nature of the differential display technique in identifying differential gene expression. This method offers a means to identify new genes of biological interest in human brain tumors such as oncogenes, tumor suppressor genes, and tumor-specific markers.

Personality change in head trauma: a validity study of the Neuropsychology Behavior and Affect Profile.

This study represents the first attempt to cross validate and report on the Neuropsychology Behavior and Affect Profile (NBAP) using closed head injury (CHI) participants. The NBAP is designed to measure emotional functioning before and following a brain event. Two CHI samples, differing primarily by method of ascertainment, were compared to a group of normal controls. Results provided support for concurrent and predictive validity of the NBAP across both CHI samples. Significantly higher levels of postinjury emotional functioning in clinic-referred CHI patients compared to CHI individuals not seeking treatment (strictly research participants) was demonstrated. A surprising finding was that pre-injury emotional levels of clinic-referred subjects were rated as less severe than that of controls. Based on this finding, the possibility of a gradient effect was discussed in which raters appeared to place selectively greater weight on current condition, while simultaneously making premorbid levels less severe than they really were. Results were discussed in the context of study limitations and directions for further research.

Frontal lobe functioning in geriatric and non-geriatric samples: an argument for multimodal analyses.

The present investigation examines specific aspects of frontal functioning across geriatric and nongeriatric cohorts. Subjects included 193 nongeriatric male pilots (mean age: 48.29 (SD = 6.79); mean education: 15.93 years (SD = 1.86)), and 68 geriatric males and females (mean age: 78.38 (SD = 5.07); mean education: 13.68 (SD = 2.53)). The results of a series of general linear model multivariate one-way analyses revealed poorer performance on frontal measures in the geriatric sample, although no differences were noted between the male and female samples. In contrast, variable interrelations, as assessed by a parametric statistic of betweengroup factor similarity, indicated a noteworthy similarity of factors between the geriatric and nongeriatric groups, and dissimilarities between the factor structures for males and geriatric females. These findings not only support the presence of age-related differences in frontal performance for the domains tested, they suggest the need to examine frontal functioning by multiple methods, as differences in frontal functioning may exist between groups that are undetected by analyses based on intergroup score differences or predictor-criterion correlations alone

Evaluation of two new neuropsychological tests designed to minimize cultural bias in the assessment of HIV-1 seropositive persons: a WHO study.

In the course of the preparatory work for the WHO cross-cultural study on the neuropsychiatric aspects of HIV-I infection, two new neuropsychological tests (the WHO/UCLA Auditory Verbal Learning Test and the Color Trails 1 & 2) were developed. The evaluation of these tests was performed at four sites, two in developed and two in developing countries. The data obtained suggest that the tests are more culture fair than others currently used to assess the same functional domains, that they are sensitive to HIV-1-associated cognitive impairment, and that this sensitivity "holds" across different cultures.

Alternate forms of the Auditory-Verbal Learning Test: issues of test comparability, longitudinal reliability, and moderating demographic variables.

The present investigation examines the alternate-form and longitudinal reliability of two versions of the Auditory-Verbal Learning Test (AVLT) on a large, multiregional, healthy male sample. Subjects included 2,059 bisexual and homosexual HIV-seronegative males recruited from the Multicenter AIDS Cohort Study from centers in Baltimore, Chicago, Los Angeles, and Pittsburgh. The findings revealed no significant differences between forms upon initial or 1-year longitudinal administration, supporting the equivalence of the two versions. However, significant practice effects were noted longitudinally, arguing for the need of appropriate retest normative data. Furthermore, as age, ethnicity, and education were found to significantly affect test performance, it is recommended that normative data be interpreted according to these variables. In addition to providing normative and longitudinal data, this investigation presents information concerning the use and limitations of the alternate forms of the AVLT.

Assessment of life events during adolescence: the use of self-report inventories.

The assessment of stressful life events during adolescence is important to both research and clinical practice. Stressful events are studied to determine their etiological significance in physical and mental illnesses, and also their relevance in the clinical assessment of individual patients. In recent years, a number of self-report inventories of life events for adolescents have been developed, some very carefully, others as one-time endeavors. This article reviews these measures, with an emphasis on the conceptual and methodological issues which created problems in earlier inventories. These issues need to be considered when choosing an instrument to study or assess stressful life events in adolescents.

[Central visual fields in pure alexia "without hemianopsia"--visual dysfunction in the right hemifield, and alexia for "kana" words in the left].

Following a left occipito-temporal subcortical hematoma, a 57-year-old, right-handed man developed pure alexia that was more prominent in kana words, especially in kana nonwords, than in kanji letters. Although a kinetic perimetry with a Goldmann perimeter showed his visual fields to be full, a static perimetry with a Humphrey visual field analyzer disclosed decreased visual sensitivity in the right visual field in its central 30 degrees. In addition, a tachnistoscopic examination with Landolt rings revealed his visual acuity (the ability of two points discrimination) to have decreased in the right half of his central visual filed in its 3 degrees. In the right central vision, he was unable to recognize the letters, pictures or colors presented by the tachistoscope. Concerning the reading, the more letters in kana words or the higher the number of strokes in kanji letters, the more difficulty he experienced in orally reading both kana and kanji. On the contrary, in the left central vision, kanji reading was not so affected by an increased number of strokes as the kana-word reading which became difficult when the number of the letters increased. CT scan showed subcortical hematoma in the left occipitotemporal region. Magnetic resonance imaging 3 months after onset revealed a localized injury in the region between the left postero-inferior temporal lobe and the infero-lateral occipital lobe, including the fusiform gyrus. None of the splenium, the lingual gyrus or the optic area were affected. The spared structures also included the angular gyrus, the Wernicke area and their subcortical white matter.(ABSTRACT TRUNCATED AT 250 WORDS)