Search

Copyright of Istanbul Gelisim University Journal of Health Sciences / İstanbul Gelişim Üniversitesi Sağlık Bilimleri Dergisi is the property of Istanbul Gelisim Universitesi Saglik Bilimleri Yuksekokulu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Preoperative planning is important for the osteosynthesis of distal radius fractures. Challenges arise for patients presenting with bilateral wrist injuries or a history of contralateral wrist injuries. In such cases, the estimation of the distal radius morphology and the determination of the plate size from the preoperative physical characteristics could prove beneficial. The objective of this study was to investigate the correlation between the physical characteristics and the morphology of the distal radius articular surface. A total of 79 wrist computed tomography (CT) images (41 women and 38 men) were evaluated. Physical characteristics, such as height, weight, and body mass index (BMI), were recorded. Three-dimensional CT analysis was performed to investigate the transverse and anteroposterior diameters of the distal radius. Pearson's correlation coefficient was used to assess the relationships between height, weight, and BMI and the transverse and anteroposterior diameters of the distal radius. A moderate to strong correlation was found in the overall analysis between body height and transverse diameter (r = 0.66). There were also moderate correlations between body height and anteroposterior diameter (r = 0.45) as well as weight and transverse diameter (r = 0.41), both of which were statistically significant ( p < 0.001). Our findings indicate a statistically significant correlation between height, weight, and morphology of the distal radius. When analyzed by sex, the correlation between body height and the transverse diameter of the distal radius was found to be relatively strong in women (r = 0.47, p = 0.002), suggesting that it could be a useful indicator for preoperative planning, such as estimating plate size.

In cases of distal radius fractures, the fixation of the volar lunate facet fragment is crucial for preventing volar subluxation of the carpal bones. This study aims to clarify the sex differences in the volar morphology of the lunate facet of the distal radius and its relationship with the transverse diameter of the distal radius. Sixty-four CT scans of healthy wrists (30 males and 34 females) were evaluated. Three-dimensional (3D) images of the distal radius were reconstructed from the CT data. We defined reference point 1 as the starting point of the inclination toward the distal volar edge, reference point 2 as the volar edge of the joint on the bone axis, and reference point 3 as the volar edge of the distal radius lunate facet. From the 3D coordinates of reference points 1 to 3, the bone axis distance, volar-dorsal distance, radial-ulnar distance, 3D straight-line distance, and inclination angle were measured. The transverse diameter of the radius was measured, and its correlations with the parameters were evaluated. It was found that in males, compared to females, the transverse diameter of the radius is larger and the protrusion of the volar lunate facet is greater. This suggests that the inclination of the volar surface is steeper in males and that the volar locking plate may not fit properly with the volar cortical bone of the lunate facet, necessitating additional fixation.

Aims: Non-dilated left ventricular cardiomyopathy (NDLVC) was proposed as a new category of cardiomyopathy that included patients with non-left ventricular (LV) dilatation, LV wall motion abnormality, or LV scar. However, the clinical background and event rates of NDLVC were unclear. The aim of this study was to examine the characteristics and event rates of patients with NDLVC and reduced LV ejection fraction (NDLVC-REF) in comparison with those with dilated cardiomyopathy (DCM)., Methods and Results: We retrospectively included 363 patients with newly diagnosed non-ischaemic cardiomyopathy and reduced LV ejection fraction (<50%) between December 2004 and January 2018. Patients who did not have LV dilatation (LV dimension index of ≦31 mm/m 2 in men and ≦34 mm/m 2 in women) were categorized as NDLVC-REF (n = 80, 22.2%), and the remaining patients were categorized as DCM. Cardiac events were defined as sudden cardiac death and rehospitalization for heart failure. Patients with NDLVC-REF had a higher prevalence of atrial fibrillation and a higher LV ejection fraction than those with DCM at baseline. LV ejection fraction was higher and LV end-diastolic diameter was smaller in patients with NDLVC-REF than in those with DCM at all time points after diagnosis. During the median follow-up period of 68.8 months (interquartile range: 33.0-93.7 months), 44 patients experienced cardiac events. The Kaplan-Meier curves showed no significant differences in the probability of cardiac events among NDLVC-REF and DCM patients (P = 0.349). However, patients with NDLVC-REF and LV dilatation after diagnosis (14%) had a higher risk of cardiac events than those with NDLVC-REF without LV dilatation (P = 0.049)., Conclusions: There was no significant difference in the incidence of cardiac events between NDLVC-REF and DCM. Among NDLVC-REF patients, 18% of patients who showed LV dilatation after diagnosis had poor outcomes. Therefore, both NDLVC-REF and DCM patients may require equivalent attention to follow-up and regular assessment of LV function., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Determining the type of amyloid deposits is clinically important for choosing the specific therapies for cardiac amyloidosis., Case Summary: A 78-year-old woman who had been experiencing fluid retention and dyspnoea on exertion for 6 months was referred to our hospital for the management of heart failure with left ventricular hypertrophy. Since 99m Tc-hydroxymethylene diphosphonate scintigraphy showed mild cardiac uptake and significant elevation of serum free lambda chain (with a difference of 263 mg/L in free light chain), we suspected immunoglobulin light-chain amyloidosis (AL), and endomyocardial biopsy was performed. The deposit site within the myocardial tissue exhibited positive for Congo red staining and transthyretin immunostaining, however negative or non-specific for light-chain immunostaining including lambda and kappa staining. Genetic testing confirmed a mutation in V122I, variant-type transthyretin amyloidosis (ATTRv). Despite the administration of patisiran, her condition exhibited progressive deterioration. Additionally, she displayed macroglossia, an atypical manifestation in ATTRv amyloidosis. Further biopsies from tongue and abdominal wall fat culminated in a final diagnosis: the coexistence of ATTRv and AL (of the lambda type). Although treatment with melphalan and dexamethasone was started, she passed away 24 months after the initial visit. When the endomyocardial biopsy specimen underwent mass spectrometry as a post hoc analysis, both ATTR and AL amyloid were significantly detected., Discussion: Coexistence of ATTRv and AL within cardiac amyloidosis is extremely uncommon. In situations where incongruities arise between the amyloid type determined via immunohistochemistry findings and the amyloid type assumed based on other clinical findings, mass spectrometry should be considered., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Objectives: Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors have been approved as an oral drug for treating anemia in chronic kidney disease (CKD). However, the clinical effect of HIF-PH inhibitors in patients with heart failure (HF) is unclear. Thus, this study investigated the effect of HIF-PH inhibitors in patients with HF and CKD. Materials and Methods: Thirteen patients with HF complicated by renal anemia who were started on vadadustat were enrolled. Clinical parameters were compared before and 1 month after vadadustat was started. Results: The mean left ventricular ejection fraction was 49.8 ± 13.9%, and the mean estimated glomerular filtration rate was 29.4 ± 10.6 mL/min/1.73 m 2 . The hemoglobin level was significantly increased (9.7 ± 1.3 mg/dL vs. 11.3 ± 1.3 mg/dL, p < 0.001), and the N-terminal prohormone of B-type natriuretic peptide was significantly decreased after the introduction of vadadustat [4357 (2651-15182) pg/mL vs. 2367 (1719-9347) pg/mL, p = 0.002]. Furthermore, the number of patients with New York Heart Association functional class ≥ 3 was also decreased after the introduction of vadadustat [8 (61.5%) vs. 1 (7.7%), p = 0.008]. No thromboembolic adverse events or new tumors were observed in any patient during the study period. Conclusions: The introduction of vadadustat in patients with HF complicated by renal anemia led to improvements in anemia and symptoms of HF.

Background: Clinical characteristics and the risk of cardiovascular events in patients with cardiac sarcoidosis (CS) according to the age of initial diagnosis are unclear., Methods: This study is a sub-analysis of the ILLUMINATE-CS registry, which is a retrospective, multicenter registry that enrolled patients with CS between 2001 and 2017. Patients were divided into three groups according to the tertile of age at the time of initial diagnosis of CS. The study compared the clinical background at the time of CS diagnosis and the incidence rate of cardiac events across age categories., Results: A total of 511 patients were analyzed in this study. In baseline, older patients were more likely to be female. History of hypertension, heart failure admission, and atrioventricular block were more common in patients with older age. There was no significant difference in the history of ventricular arrhythmias and left ventricular ejection fraction among all age groups. During a median follow-up period of 3.2 [IQR: 1.7-4.2] years, 35 deaths, 56 heart failure hospitalization, and 98 fatal ventricular arrhythmias was observed. The incidence rate of all-cause death and heart failure hospitalization was significantly higher in patients with older age (p < 0.001), while there was no significant difference in the incidence rate of ventricular arrhythmia among age groups (p = 0.74)., Conclusions: In patients with CS, the risk of all-cause death and heart failure hospitalization was higher in older patients compared with other age groups; however, the risk of ventricular arrhythmia was comparable across all age groups., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Yuya Matsue received an honorarium from Otsuka Pharmaceutical Co. and Novartis Japan. Dr. Takahiro Okumura received honoraria from Ono Yakuhin, Otsuka, Novartis, and Astrazeneca and research grants from Ono Yakuhin, Amgen Astellas, Pfizer, Alnylam, and Alexion (not in connection with the submitted work). The authors have no conflicts of interest to declare., (© 2023 The Author(s).)

The present study attempted to define the three-dimensional (3D) locations of reference points and standard measures of the distal radius of a normal wrist joint. One hundred wrists from 50 males and 50 females who matched the age distribution (19−95 years old, mean: 56.0 years old) were evaluated. Computed tomography (CT) images of normal wrist joints acquired for comparison with the affected side were used. The absence of a previous history and complaints in the unaffected wrist was confirmed in an interview and with medical records. Three-dimensional images of the distal radius were reconstructed using the data obtained from CT scans. The site at which the major axis of the radial diaphysis contacted the distal radius joint surface was defined as the origin. The 3D coordinates of reference points for the radial styloid process (1), sigmoid notch volar edge (2), and sigmoid notch dorsal edge (3) as well as the barycenter for the joint surface and joint surface area were evaluated. A slope of the line connecting coordinates 1−2 in the coronal plane was evaluated as the 3D radial inclination (3DRI) and that connecting coordinates 2−3 in the sagittal plane as the 3D palmar tilt (3DPT). Each measurement value was compared between males and females. The positions of each reference point from the origin were as follows: (1) 14.2 ± 1.3/12.6 ± 1.1 mm for the distal-palmar-radial position; (2) 19.3 ± 1.3/16.9 ± 1.3 mm for the proximal-palmar-ulnar position; (3) 15.6 ± 1.4/14.1 ± 0.9 mm for the proximal-dorsal-ulnar position; and (barycenter) 4.1 ± 0.7/3.7 ± 0.7 mm for the proximal-volar-ulnar position for males and females, respectively. The areas of the radius articular surface were 429.0 ± 67.9/347.6 ± 44.6 mm2 for males and females, respectively. The 3DRI and 3DPT were 24.2 ± 4.0/25.7 ± 3.1° and 10.9 ± 5.1/13.2 ± 4.4° for males and females, respectively. Significant differences were observed in all measurement values between males and females (p < 0.01). The reference points and measured values obtained in the present study will serve as criteria for identifying the dislocation direction and reduction conditions of distal radius fractures in 3D images.

Introduction: Fragility fracture of the pelvis (FFP), generally involving Rommens and Hoffman classification type IVb (H-shaped) requires spinopelvic fixation (SPF). We report the clinical outcome of sacroiliac rod fixation (SIRF) for FFP type IVb in a case series., Materials and Methods: In this retrospective observational study, six patients (mean age, 80.3 years; range, 74-85 years) with FFP type IVb who underwent SIRF since October 2019 and could be followed up for ≥1 year postoperatively were included. All patients were injured in low-energy falls, a patient had a femoral neck fracture, and other had a humeral neck fracture and distal radius fracture., Results: The mean (range) operative time was 135 (98-200) min, and mean blood loss was 103 (80-130) g. All patients achieved bone union in an average of 4.3 months. No implant failure or surgical site infection requiring reoperation occurred. No patient complained of iliac screw irritation or requested removal. One patient developed a T12 vertebral fracture at 3 weeks postoperatively. The mean final follow-up period was 17.8 months (13-22 months) and mean final modified Majeed Score (maximum 76 points as the items "work" and "sexual intercourse" were omitted for this study) was 71.7 (56-76)., Conclusions: SIRF is a less invasive surgical technique than SPF that uses only an S1 pedicle screw and iliac screw. SIRF using the "within ring" concept showed good clinical outcome in FFP type IVb., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Although cardiac resynchronization therapy (CRT) provided functional and clinical improvement in patients with heart failure (HF) and electrical intraventricular conduction disturbances, some patients had re-worsening left ventricular (LV) function after a favorable CRT response. We analyzed the clinical variables and cardiac outcomes associated with this re-worsening LV function after CRT., Methods: In this study, 71 patients with CRT response who received CRT between 2006 and 2017 were included. CRT response was defined as a "≥ 10% improvement in LV ejection fraction (LVEF) on follow-up." Patients were classified into two groups: (i) persistent: (n = 48, 68%), defined as those with a CRT response and (ii) re-worsening: (n = 23, 32%), consisting of those who fell out of the definition of a CRT response after an initial CRT response., Results: Half of the patients in the re-worsening group failed to maintain a CRT response from two years upwards. A longer duration from HF diagnosis to CRT implantation, nonspecific intraventricular conduction delay (NIVCD) on electrocardiogram at CRT implantation, and a lower increased LVEF at initial CRT response were independent predictors for the re-worsening group. Patients in the re-worsening group had a higher incidence rate for HF hospitalization and cardiac deaths, compared with those in the persistent group., Conclusion: One-third of CRT responders experienced re-worsening LVEF, which was associated with poor outcomes. CRT responders with NIVCD, longer HF duration, and a lower increased LVEF at initial CRT response should be monitored with caution., (Copyright © 2021. Published by Elsevier Ltd.)

Denaturation of actin and myosin in myofibrils induced by heating at 50°C was investigated to reveal the mechanism of irreversible liberation of actin from myofibrils on heating at lower temperatures than conventional cooking. Denaturation of these proteins was determined by Mg 2+ -ATPase (adenosine triphosphatase) and Ca 2+ -ATPase activities. When minced meat was heated for 20 min, actin was liberated accompanying denaturation of 80% of actin and 50% of myosin. Heating of the myofibrillar fraction (MFF) isolated from meat homogenate induced much slower denaturation of actin than myosin. When MFF was heated with sarcoplasmic fractions, denaturation of actin was facilitated, suggesting that sarcoplasmic fractions contain factors to facilitate actin denaturation. Inosine-5'-monophosphate, a component of sarcoplasmic fractions, was shown to have no effect on actin and myosin denaturation. These results suggest that heating meat at 50°C dissociates binding ('Bond A') between actin and myosin participating in ATPase activities, resulting in denaturation of both proteins under influence of sarcoplasmic components. Although denaturation of actin and myosin disrupted Bond A, actin was not liberated simultaneously, suggesting the presence of another bond ('Bond B', more heat-stable than Bond A) between both proteins and necessity of disruption of Bond B for actin release from myofibrils., (© 2017 Japanese Society of Animal Science.)

Alphaproteobacterium strain Q-1 is able to oxidize iodide (I(-)) to molecular iodine (I(2)) by an oxidase-like enzyme. One of the two isoforms of the iodide-oxidizing enzyme (IOE-II) produced by this strain was excised from a native polyacrylamide gel, eluted, and purified. IOE-II appeared as a single band (51 kDa) and showed significant in-gel iodide-oxidizing activity in sodium dodecyl sulfate-polyacrylamide gel electrophoresis without heat treatment. However, at least two bands with much higher molecular masses (150 and 230 kDa) were observed with heat treatment (95°C, 3 min). IOE-II was inhibited by NaN(3), KCN, EDTA, and a copper chelator, o-phenanthroline. In addition to iodide, IOE-II showed significant activities toward phenolic compounds such as syringaldazine, 2,6-dimethoxy phenol, and p-phenylenediamine. IOE-II contained copper atoms as prosthetic groups and had UV/VIS absorption peaks at 320 and 590 nm. Comparison of several internal amino acid sequences obtained from trypsin-digested IOE-II with a draft genome sequence of strain Q-1 revealed that the products of two open reading frames (IoxA and IoxC), with predicted molecular masses of 62 and 71 kDa, are involved in iodide oxidation. Furthermore, subsequent tandem mass spectrometric analysis repeatedly detected peptides from IoxA and IoxC with high sequence coverage (32 to 40%). IoxA showed homology with the family of multicopper oxidases and included four copper-binding regions that are highly conserved among various multicopper oxidases. These results suggest that IOE-II is a multicopper oxidase and that it may occur as a multimeric complex in which at least two proteins (IoxA and IoxC) are associated.

Background: Preadministration of high-affinity humanized anti-HIV-1 mAb KD-247 by passive transfer provides sterile protection of monkeys from heterologous chimeric simian/human immunodeficiency virus infection., Methods: Beginning 1 h, 1 day, or 1 week after simian/human immunodeficiency virus-C2/1 challenge (20 50% tissue culture infective dose), mature, male cynomolgus monkeys received multiple passive transfers of KD-247 (45 mg/kg) on a weekly basis for approximately 2 months. Concentrations and viral loads were measured in peripheral blood, and CD4 T-cell counts were examined in both peripheral blood and various lymphoid tissues., Results: Pharmacokinetic examination revealed similar plasma maintenance levels ranging from 200 to 500 microg/ml of KD-247 in the three groups. One of the six monkeys given KD-247 could not maintain these concentrations, and elicitation of anti-KD-247 idiotype antibody was suggested. All monkeys given KD-247 exhibited striking postinfection protection against both CD4 T-cell loss in various lymphoid tissues and atrophic changes in organs compared with control group animals treated with normal human immunoglobulin G. The KD-247-treated groups were also partially protected against plasma viral load elevation in peripheral blood samples, although the complete protection previously reported with preadministration of this mAb was not achieved., Conclusion: Postinfection passive transfer of humanized mAb KD-247 with strong neutralizing capacity against challenged virus simian/human immunodeficiency virus-C2/1 protected CD4 T cells in lymphoid organs.

An antibody response capable of neutralizing not only homologous but also heterologous forms of the CXCR4-tropic human immunodeficiency virus type 1 (HIV-1) MNp and CCR5-tropic primary isolate HIV-1 JR-CSF was achieved through sequential immunization with a combination of synthetic peptides representing HIV-1 Env V3 sequences from field and laboratory HIV-1 clade B isolates. In contrast, repeated immunization with a single V3 peptide generated antibodies that neutralized only type-specific laboratory-adapted homologous viruses. To determine whether the cross-neutralization response could be attributed to a cross-reactive antibody in the immunized animals, we isolated a monoclonal antibody, C25, which neutralized the heterologous primary viruses of HIV-1 clade B. Furthermore, we generated a humanized monoclonal antibody, KD-247, by transferring the genes of the complementary determining region of C25 into genes of the human V region of the antibody. KD-247 bound with high affinity to the "PGR" motif within the HIV-1 Env V3 tip region, and, among the established reference antibodies, it most effectively neutralized primary HIV-1 field isolates possessing the matching neutralization sequence motif, suggesting its promise for clinical applications involving passive immunizations. These results demonstrate that sequential immunization with B-cell epitope peptides may contribute to a humoral immune-based HIV vaccine strategy. Indeed, they help lay the groundwork for the development of HIV-1 vaccine strategies that use sequential immunization with biologically relevant peptides to overcome difficulties associated with otherwise poorly immunogenic epitopes.

In an accompanying report (Y. Eda, M. Takizawa, T. Murakami, H. Maeda, K. Kimachi, H. Yonemura, S. Koyanagi, K. Shiosaki, H. Higuchi, K. Makizumi, T. Nakashima, K. Osatomi, S. Tokiyoshi, S. Matsushita, N. Yamamoto, and M. Honda, J. Virol. 80:5552-5562, 2006), we discuss our production of a high-affinity humanized monoclonal antibody, KD-247, by sequential immunization with V3 peptides derived from human immunodeficiency virus type 1 (HIV-1) clade B primary isolates. Epitope mapping revealed that KD-247 recognized the Pro-Gly-Arg V3 tip sequence conserved in HIV-1 clade B isolates. In this study, we further demonstrate that in vitro, KD-247 efficiently neutralizes CXCR4- and CCR5-tropic primary HIV-1 clade B and clade B' with matching neutralization sequence motifs but does not neutralize sequence-mismatched clade B and clade E isolates. Monkeys were provided sterile protection against heterologous simian/human immunodeficiency virus challenge by the passive transfer of a single high dose (45 mg per kg of body weight) of KD-247 and afforded partial protection by lower antibody doses (30 and 15 mg per kg). Protective neutralization endpoint titers in plasma at the time of virus challenge were 1:160 in animals passively transferred with a high dose of the antibody. The antiviral efficacy of the antibody was further confirmed by its suppression of the ex vivo generation of primary HIV-1 quasispecies in peripheral blood mononuclear cell cultures from HIV-infected individuals. Therefore, KD-247 promises to be a valuable tool not only as a passive immunization antibody for the prevention of HIV infection but also as an immunotherapy for the suppression of HIV in phenotype-matched HIV-infected individuals.

A full length cDNA of feline interleukin(IL)-12 p35 and p40 subunits was cloned. By transferring the plasmids containing both the subunit genes to mammalian cells, we expressed biologically active feline IL-12. The expressed feline IL-12 has interferon-gamma-inducing activity against both human and feline peripheral blood mononuclear cells (PBMC) and stimulates cytotoxic T lymphocyte activity against herpes simplex virus-infected human PBMCs. There were two kinds of molecules (p75, p80) in the purified recombinant feline IL-12, and both molecules exhibited biological activity. The difference between p75 and p80 was the degree of the glycosylation of the p35 chain. Moreover, when we modified the cDNA of p35 by changing some codons and deleted the 5' and 3' non-coding regions, the expression level of IL-12 increased about 100 fold.

The sequences of the V3 loop and surrounding regions of human immunodeficiency virus type-1 from a father-to-mother-to-infant trimmer were studied and the horizontal and vertical transmissions compared. The father's virus was variable for reactivity with neutralizing antibody and sequences of the V3 loop central core sequence. In contrast, the mother's viral sequences were much less diverse and reacted with a virus neutralizing antibody. The infant's viral sequences were also less diverse than those of the father, and N-glycosylation sites were conserved. By phylogenetic analysis, the major clone, of which V3-peptide reacted with the neutralizing antibody, was found to be transmitted from the mother to her infant; however, the mutated minor clones did not bind to the antibody. These findings suggest that both horizontal and vertical virus transmission were selective, and that the clonally transmitted virus in infants mutates more rapidly than viruses in the mother, to whom the virus was horizontally transmitted.

In order to elucidate the significance of the adenoma-carcinoma sequence in gastric carcinogenesis from a genetic point of view, we examined microsatellite alterations (replication error and loss of heterozygosity) on chromosomes 2p (D2S123), 3p (D3S1317), 5q (D5S409), 9p (IFNA), and 13q (D13S153) as well as p53 gene mutations in 13 adenomas and 23 differentiated adenocarcinomas including 8 early carcinomas of the stomach. Replication error was detected in only one of the adenomas (8%, 1/13) at the D5S409 locus and in none at the other loci, and loss of heterozygosity was also an infrequent event found in one adenoma (14%, 1/7 informative cases) at D5S409 and in none at the other loci. A p53 gene mutation was detected in one (8%, 1/13) of the adenomas. Thus, microsatellite alterations and p53 gene mutations are rare events in adenomas. In differentiated adenocarcinomas, replication error was detected in 4 (17%, 4/23) at single or multiple loci, and loss of heterozygosity was observed frequently at D3S1317 (25%, 3/12), D5S409 (67%, 6/9), and IFNA (26%, 5/19). Mutations in the p53 gene were detected in 9 (39%, 9/23) of the differentiated adenocarcinomas. Microsatellite alterations on several chromosomes and mutations in the p53 gene were frequent in differentiated adenocarcinomas, even those at an early stage. These results suggest that the adenoma-carcinoma sequence is relatively rare in gastric carcinogenesis, and that the majority of differentiated adenocarcinomas of the stomach may develop through a de novo pathway.

A putative tumor suppressor gene, p16 (MST1; multiple tumor suppressor 1/CDK4I; cyclin-dependent kinase 4 inhibitor), was isolated and mapped on the short arm of chromosome 9 (9p). The significance of p16 mutations in gastric tumorigenesis was examined by assessing p16 mutations as well as loss of heterozygosity (LOH) on 9p in 13 gastric adenomas and 45 adenocarcinomas. LOH on 9p (IFNA; alpha-interferon locus) was detected in 22% (5/23 informative cases) of differentiated adenocarcinomas, 10% (1/10) of undifferentiated carcinomas and none (0/6) of the adenomas. Although we found a sequence polymorphism at the second position of codon 99 (CGC/CAC) of the p16 in one gastric adenoma patient, no somatic mutations were detected in any of the gastric adenomas or adenocarcinomas. These results suggest that p16 mutations probably do not contribute to gastric tumorigenesis. However, these data suggest that another tumor suppressor gene on 9p (near the IFNA locus) may contribute to the progression of differentiated adenocarcinoma of the stomach.

4-Hydroxyphenylpyruvic acid dioxygenase is an important enzyme in tyrosine catabolism in most organisms. From porcine and human liver cDNA libraries we isolated complementary DNA inserts for the enzyme. Protein sequence analysis of the porcine enzyme revealed a block of the amino terminus of the mature enzyme. Comparison of the amino acid sequence determined by Edman degradation of peptides derived from porcine liver 4-hydroxyphenylpyruvic acid dioxygenase with the nucleotide sequences revealed the primary structure of the porcine and human enzymes. The mature human and porcine enzymes have an 89% amino acid sequence identity in amino acid residues and are composed of 392 amino acid residues. A computer-assisted homology search revealed that the enzyme is 88% identical in amino acid sequence to rat liver-specific alloantigen F. A monoclonal antibody (mob 51), which can immunoprecipitate both the human and porcine enzymes, was developed. Cultured BMT-10 cells transfected with the cDNA insert of the human enzyme, using the expression vector pCAGGSneodE, produced a polypeptide with an M(r) of 43,000, which was immunoprecipitated with mob 51. Enzymic activity of the enzyme was detected in the transfected cells but not in the mock transfected cells. These findings suggest that the human 4-hydroxyphenylpyruvic acid dioxygenase is a homodimer of two identical subunits with an M(r) of 43,000. Liver-specific alloantigen F seems to be closely related to the enzyme or possibly to the subunit of the enzyme itself. Elucidation of the complete amino acid sequence of the enzyme is expected to reveal structure-function relationships of this metabolically important enzyme and to shed light on inherited disorders related to tyrosine metabolism, especially tyrosinemia types 1 and 3.

The acquired immunodeficiency syndrome (AIDS) is the late-stage clinical manifestation of long-term persistent infection with the human immunodeficiency virus type 1 (HIV-1). Immune responses directed against the virus and against virus-infected cells during the persistent infection fail to mediate resolution of the infection. As a result, a successful AIDS vaccine must elicit an immune state that will prevent the establishment of the persistent infection following introduction of the virus into the host. The third hypervariable (V3) domain of the HIV-1 gp120 envelope glycoprotein is a disulphide-linked closed loop of about 30 amino acids which binds and elicits anti-HIV-1 type-specific virus-neutralizing antibodies. The in vitro characteristics of anti-V3 domain antibody suggest that this antibody could by itself prevent HIV-1 infection in vivo, an idea supported by chimpanzee challenge studies in which protection against the HIV-1 persistent infection seemed to correlate with the presence of anti-V3 domain antibody. Here we directly demonstrate the protective efficacy of anti-V3 domain antibody in vivo and propose that this antibody is potentially useful as both a pre- and post-exposure prophylactic agent.

New latex particles for immunologic agglutination reaction were prepared by a seeded polymerization technique for the emulsifier-free copolymerization of styrene and glycidyl methacrylate. The surface of the latex particles was presumed to be dotted with hydrophilic domains, giving stability to the particles. The remaining areas, to which many antigens or antibodies were strongly adsorbed, were hydrophobic. Various groups of the glycidyl methacrylate-styrene latex particles were coated with human immunoglobulin G, and immunologic agglutinating potencies were compared by the box-titration method. Immunologic reactivities of the latex particles decreased with an increase of glycidyl methacrylate content at concentrations of 1 mol% or higher. Latex particles containing 0.5 to 0.75 mol% GMA caused strong immunologic agglutination besides showing good stability, indicating the availability of these latex particles. Glycidyl methacrylate-free polystyrene latex particles caused non-specific agglutination, while the immunologic agglutinating ability of glycidyl methacrylate-styrene latex particles, prepared by the unseeded polymerization technique was weak.

The chemotherapeutic properties of miloxacin (5,8-dihydro-5-methoxy-8-oxo-2H-1,3-dioxolo-[4,5-g]quinoline-7-carboxylic acid) have been compared with those of oxolinic acid and nalidixic acid. The in vitro activities of miloxacin (minimum inhibitory concentrations) against a variety of gram-negative bacteria, especially Enterobacteriaceae and Haemophilus, were comparable to those of oxolinic acid and 8 to 16 times greater than those of nalidixic acid. Miloxacin was more active than oxolinic acid against some anaerobes and less active against staphylococci. Miloxacin exhibited significant activities when administered orally to mice infected with Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, or Serratia marcescens. Its efficacy was comparable to that of oxolinic acid and two to four times greater than that of nalidixic acid. Miloxacin was less active against a Pseudomonas aeruginosa infection and inactive at the maximum test doses against a Streptococcus pyogenes infection.

Nuclei of murine T lymphocytes or B lymphocytes were purified and transferred into lethally irradiated whole spleen cells or B or T lymphocytes by means of polyethyleneglycol-mediated cell fusion. Transfer of lymphocyte nuclei could save the irradiated cells from cell death, and such reconstituted cells could respond to mitogens. The present study showed that nuclei of T cells could be activated in the concanavalin A-stimulated T cell cytoplasms but not in the lipopolysaccharide-stimulated B cell cytoplasms. On the other hand, nuclei of B cells were activated in the lipopolysaccharide-stimulated B cells but not in the concanavalin A-stimulated T cell cytoplasms. These data suggested that a specific interaction between cytoplasm and nucleus might exist in the activation of nuclei of each lymphocyte subset.

PC-904, sodium 6-{d(-)-alpha-(4-hydroxy-1,5-naphthyridine-3-carboxamido) phenylacetamido}-penicillanate, is a novel semisynthetic penicillin derivative that possesses a broad spectrum of in vitro and in vivo antibacterial activities. In low concentrations, PC-904 inhibits growth against large proportions of the gram-positive and gram-negative organisms susceptible to carbenicillin and gentamicin. In addition, PC-904 is several times more potent than carbenicillin against organisms such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Proteus vulgaris, Shigella, Salmonella, Neisseria gonorrhoeae, and Bacteroides fragilis. Most striking are the inhibitory effects of PC-904 against P. aeruginosa and K. pneumoniae. Against these two clinical isolates, PC-904 is, respectively, 35 and 100 times more active than carbenicillin. The minimum inhibitory concentrations of PC-904 against P. aeruginosa are comparable to those of gentamicin. PC-904 acts bactericidally. The effect of inoculum size on the antibacterial activity is often small and generally comparable to carbenicillin. The rate of binding to serum protein is high (88 to 98%), but the effect of the addition of serum on the drug's activity is not marked, because such binding is reversible. It is confirmed that PC-904 has a very potent in vivo antibacterial activity against gram-negative and gram-positive organisms. Against systemic infections with P. aeruginosa, K. pneumoniae, and E. coli in mice, PC-904 is 7 to 10 times, over 8 times, and 2 to 15 times more active than carbenicillin, respectively.