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Biomedical subjects

R Ochs

Publications and source records attributed to R Ochs.

15 recordsLinked to original sources

A comparative study of alpidem, a nonbenzodiazepine, and lorazepam in patients with nonpsychotic anxiety.

The use of benzodiazepines for generalized anxiety disorder (GAD) is a safe and effective treatment; however, their potential to produce dependence and impair psychomotor and cognitive functions is a drawback. In this study the efficacy and safety of alpidem, a nonbenzodiazepine, was assessed. Thirty patients who met DSM-III-R criteria for GAD were randomized to either alpidem (225 mg), lorazepam (4.5 mg), or placebo. The primary efficacy measure was the Hamilton Rating Scale for Anxiety (HAM-A). A repeated measures multivariate analysis of variance (MANOVA) was used to determine differences in HAM-A scores over time. The results showed a trend for alpidem to be more effective. Half of the alpidem group had a decrease of 50 percent or greater in their HAM-A scores with an almost equal effect on psychic and somatic symptoms. The most common side effects with alpidem and lorazepam were lightheadedness, drowsiness, and daytime tiredness. Moreover, treatment with alpidem did not manifest any withdrawal symptoms. Thus nonbenzodiazepine treatments are effective and safe for GAD.

Adult

Dose response effects of zolpidem in normal geriatric subjects.

The dose-related hypnotic effects and effects on memory, performance, and daytime alertness of zolpidem 5, 10, 15, and 20 mg were compared with those of placebo in 30 elderly non-insomniac volunteers in a randomized, placebo-controlled, three-period crossover study. Subjects were randomized into two groups and received either placebo, zolpidem 5 mg, or zolpidem 15 mg or placebo, zolpidem 10 mg, or zolpidem 20 mg for 2 consecutive nights followed by 1 night of placebo during the same 3 nights of 3 consecutive weeks. Polysomnographic results showed statistically significant decreases in sleep latency and increases in sleep efficiency at all doses. Subjective reports also showed improved sleep latency, total sleep time, and sleep quality. REM percent was slightly decreased at doses of 10 and 20 mg. No consistent effects on memory or performance were observed, and the Multiple Sleep Latency Test showed no effects on daytime sleepines. There was no objective evidence of rebound insomnia upon drug discontinuation.

Aged

Proliferation-related nucleolar antigens P145 and P120 associated with separate nucleolar elements and differences in tissue distribution.

Nucleolar antigens p145 and p120 are associated with proliferating cells (Freeman, J.W.; McRorie, D.K.; Busch, R.K.; Gyorkey, P.; Gyorkey, F.; Ross, B.E.; Spohn, W.H.; Busch, H. Cancer Res. 46:3593; 1986 and Freeman, J.W.; Busch, R.K.; Gyorkey, P.; Gyorkey, F.; Ross, B.E.; Busch, H. Cancer Res. 48:1244; 1988) and are not detectable in normal resting cells. Recent immunoelectron microscopic studies (Ochs, R.L.; Reilly, M.T.; Freeman, J.W.; Busch, H. Cancer Res. 48:6523; 1988) suggest that the two antigens have overlapping nucleolar localizations. In this study the nucleolus was physicochemically and biochemically studied to determine whether p145 and p120 were associated with a common nucleolar component. Antigen p145 was associated with 40-80 S ribonucleoprotein particles (RNPs), and the p145 antigen was not detected in HeLa cells following in situ RNAse digestion. P120 was found in a 40-80 S, RNAse resistant complex. Sequential extraction of HeLa nucleoli showed that most of antigen p145 was extractable in 10 mM Tris with 0.2% deoxycholate, whereas p120 was found in a nucleolar residue fraction requiring DNAse and high salt treatment for optimal extraction. Neither antigen p145 nor p120 was detectable in normal resting tissues. Antigen p145 was detected in all proliferating tissues examined, including a variety of malignant tumors (ten of ten), benign tissues including adenomas and hyperplasias (eight of eight), and in normal proliferating cells such as colonic epithelium and spermatogonia of the testes. Antigen p120 was not detected in all tumors, being absent in three of seven lymphomas and in one melanoma examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Nuclear

Novel nucleolar antigens in autoimmune disease.

Antinucleolar antibodies are of interest in 2 important areas, namely, autoimmune diseases and specific products involved in the "mitogenic cascade." The former have delineated a series of novel nuclear and nucleolar elements including the recently described proliferating cell nuclear antigens (PCNA), some of which are present in the nucleolus only at specific times in the G1-S phase of the cell cycle. Important new proteins such as "fibrillarin" (34 kD/pI 8.5) and a 125 kD nucleotide containing protein have been identified with antinucleolar antibodies. Protein p145 is a nucleolar PCNA that is present in growing and dividing cells but not in normal resting tissues. Antinucleolar antibodies offer powerful tools, not only for identification of specific nucleolar proteins important in the cell cycle, but also for purification of their genes and analysis of mechanisms of gene control that operate the "time windows" of the cell cycle.

Amino Acid Sequence

Studies on satellite nucleoli in human normal and leukemic lymphocytes.

Lymphocytes from normal and leukemic patients, and phytohemagglutinin-stimulated lymphocytes were investigated by means of immunofluorescence procedures and a silver reaction for the demonstration of proteins characteristic of nucleolus organizer regions in interphasic cells to provide basic information on the presence of satellite nucleoli in these cells. The results clearly indicated that satellite nucleoli are present in a limited but constant percentage of peripheral lymphocytes. An increased percentage of lymphocytes with satellite nucleoli was found only in leukemic patients and after silver staining. In contrast, a decreased percentage of satellite nucleoli was found 24 h after stimulation with phytohemagglutinin vitro. In leukemic patients, the discrepancy in the percentage of lymphocytes with satellite nucleoli between immunostained and silver-stained preparations may suggest that the silver reaction demonstrates the presence of an additional argyrophilic protein besides proteins B23 and C23, or altered forms of these proteins, which does not react with the specific antibodies.

Cell Nucleolus

Purification of an 86-70 kDa nuclear DNA-associated protein complex.

In the course of studies on nucleolar antigens, monoclonal antibodies were developed, one of which recognized an 86 kDa antigen as shown by analysis of nuclear extracts from HeLa or Namalwa cells. Immunofluorescence studies on HeLa cells showed a nucleoplasmic and phase-dependent nucleolar localization of the monoclonal antibody was decreased after digestion with DNAase I but not with RNAase A. For purification, the antigen was released from nuclei by digestion with DNAase I and then purified by chromatography on DEAE cellulose, phosphocellulose and antibody-Sepharose affinity chromatography. Interestingly, the immunoaffinity purified product contained two polypeptide chains; the immunoreactive polypeptide had an Mr of 86 000 and a pI of 6.0. The complex also contained a 70 kDa, pI 6.5 nonantigenic polypeptide in a 1:1 ratio. The overall purification of the complex was 5700-fold. Both polypeptides contained approx. 15 mol% glutamic acid and the 70 kDa polypeptide contained approx. 15 mol% serine.

Amino Acids

Immunofluorescence studies on proteins B23 and C23 in nucleoli of human lymphocytes.

Nucleoli of normal and leukemic lymphocytes were studied by cytochemical and immunofluorescence methods to provide more information on the nucleolar presence and distribution of proteins B23 and C23. Annular nucleoli of human lymphocytes represent a very convenient subject for such studies, since they consist of one centrally located large fibrillar center surrounded by RNP components. In such nucleoli, protein C23 was present mainly in the central nucleolar region and protein B23 was found mostly in the periphery. The nucleolar area immunostained for protein B23 was usually larger than that stained for protein C23. The distribution of protein C23 appeared to be similar to that of intensely stained nucleolar argyrophilic components. No substantial differences were found between the distribution of proteins B23 and C23 in nucleoli of normal and leukemic lymphocytes. In lymphocytes of patients treated with chemotherapy, the immunofluorescence was diminished for protein B23 and particularly so for protein C23.

Cell Nucleolus

Does head-turning during a seizure have lateralizing or localizing significance?

Forced lateralized head-turning, occurring as the first clinical sign in 106 epileptic seizures in 43 patients, was recorded on videotape simultaneously with the EEG. Forty-five ictal EEGs were obtained with stereotaxically implanted intracerebral electrodes. Forced head-turning was seen with seizures that had a frontal, temporal, unilateral diffuse, or a generalized onset in the EEG. Ipsilateral was as common as contralateral head-turning in all groups, including the seizures with frontal lobe onset. Initial head-turning in a seizure has no localizing or lateralizing significance.

Adolescent

Localization of nucleolar phosphoproteins B23 and C23 during mitosis.

Nucleolar phosphoproteins B23 and C23 were simultaneously localized in unsynchronized male rat-kangaroo PtK2 cells during mitosis using a mouse monoclonal antibody against protein B23 and a rabbit antibody against protein C23. The distribution of proteins B23 and C23 during mitosis was compared with the distribution of the silver staining protein. During interphase, proteins B23 and C23 were both localized to the nucleolus. As the nucleolus disappeared in prophase, the distribution of protein B23 became nucleoplasmic, whereas most of protein C23 remained associated with the disappearing nucleolus. Throughout metaphase and anaphase protein B23 was found associated with the chromosomes, whereas protein C23 seemed to disappear. When the nucleolus reformed during telophase, protein C23 appeared first in 'prenucleolar bodies' and then in the nucleolus, whereas protein B23 did not appear in the nucleolus until late telophase or early G1 phase. Silver staining during mitosis closely paralleled the distribution of protein C23, supporting previous conclusions that protein C23 is a silver staining nucleolus organizer region (NOR) protein [19, 20].

Animals

Brainstem auditory evoked responses in leukodystrophies.

Brainstem auditory evoked responses (BAERs) were recorded in seven patients with Pelizaeus-Merzbacher leukodystrophy (PMD), two with adrenoleukodystrophy (ALD), and one with metachromatic leukodystrophy (MLD). BAERs were altered in all patients, and the alterations were severe in 9 of the 10 patients. A patient with ALD who as yet had no neurologic symptoms showed only minimal abnormality of the BAERs, consisting of prolongation of the latency of wave V. In the remaining nine patients, only wave I generated in the extramedullary portion of the eighth nerve was recorded with or without a wave II. Subsequent components (III through VII) were absent. No abnormality of BAERs was observed in the 10 known carriers of PMD. The combination of BAERs and EEG is helpful in differentiating leukodystrophy from progressive gray matter diseases.

Adult

Effect of hemoglobin loads on the function and morphology of ischemic kidneys in the rat.

Male Wistar rats were used to investigate the effects of stromafree hemoglobin (200 mg Hb/100 g body weights, i.v. as a 16.4% solution) on kidney function and morphology. Ischemia of the kidney was induced by bilateral clamping of the renal pedicle. The most severe disturbances of kidney function occurred in kidneys damaged by ischemia during the peak of Hb excretion; endogenous creatinine clearance decreased to 5% of control values, serum creatinine concentration rose 6 times as high as control values, and Hb excretion in the urine was reduced. Kidney damage after Hb loading and ischemia was more severe than damage caused by ischemia alone. These results demonstrate that the vulnerability of kidneys to damage by ischemia is increased by Hb loading.

Animals

Antithymocyte gamma globulin, low-dosage cyclosporine, and tapering steroids as an immunosuppressive regimen to avoid early kidney failure in heart transplantation.

Cyclosporine is a powerful immunosuppressive agent that unfortunately has significant renal toxicity. Two risk factors associated with a high incidence of kidney failure in patients receiving cyclosporine have been described in the literature. In an effort to decrease the possibility of renal toxicity with the use of cyclosporine, we use low-dosage cyclosporine, antithymocyte gamma globulin, and tapering dosages of steroids as an immunosuppressive regimen. Twenty-one patients had orthotopic heart transplants from January 1985 to January 1986. Sixteen of 21 patients or 70% had at least one high risk factor for kidney failure. There were no episodes of acute kidney failure, and the blood urea nitrogen and creatinine levels that were recorded over an average of 8.5 months per patient did not increase significantly from preoperative values. Seventeen of 21 or 81% of the patients are alive and functioning fully. The incidence of rejection per patient was 0.9, and there were no biopsy-proven severe rejections. One patient died at 5 months; the autopsy showed generalized moderate rejection. There were 0.24 episodes of infection per patient, with one patient who died from Pneumocystis pneumonia. With this immunosuppression protocol, early postoperative kidney dysfunction was avoided. The incidences of rejection and infection were within acceptable range, and the quality of life in the 17 survivors is excellent.

Acute Kidney Injury