Quantitative determination of cell surface β-adrenoceptors in different rat skeletal muscles

In the present study, the density of cell surface beta-adrenergic receptors was determined in different skeletal muscles using the hydrophilic ligand [3H]CGP 12177. The density of beta-adrenergic receptors was highest in the slow-twitch soleus muscle (32.8+/-0.9 fmol mg dw(-1)) and lowest in the fast-twitch glycolytic white gastrocnemius (10.4+/-0.5 fmol mg dw(-1)) beta-Adrenoceptor density correlated closely with the percentage of type-I fibres (r=0.979; P<0.0001) and inversely with the percentage of type-IIB fibres (r=696; P<0.03). Incubation with isoprenaline (10 microM) for 30 min decreased the density of beta-adrenergic receptors in the cell surface from 32.9+/-0.8 to 19.3+/-0.7 fmol mg dw(-1) in the soleus and from 16.8+/-1.0 to 12.0+/-0.7 fmol mg dw(-1) in the epitrochlearis. Internalisation appeared rapid (half-time less than 5 min). To study externalisation of beta-adrenergic receptors, soleus strips were incubated 30 min with 10 microM isoprenaline and then transferred to buffer without agonist. The first incubation reduced the density to approximately 50%, the subsequent incubation without agonist increased cell surface receptor density to approximately 80% of the initial density after 1 h. No further increase was observed over the next 2 h, suggesting that some of the receptors had been degraded. Insulin or contractile activity did not influence rate of externalisation.     

Viral load,CD4 percentage,and delayed-type hypersensitivity in subjects receiving the HIY-1 Immunogen and antiviral drug therapy

Two trials of subjects inoculated with the inactivated, gp120-depleted HIV-1 Immunogen are reported. In one study, in which 19 subjects received ZDV and 8 subjects received ddI, treatment with the HIV-1 Immunogen did not affect the pharmacokinetic parameters of the antiviral drugs. In another study, 65 subjects who were previously immunized with the HIV-1 Immunogen over a mean period of 4.0 years (range, 1.2–5.4 years) received inoculations at 0 and 6 months. At some point during this 48-week study, 72% of the subjects (47/65) were receiving antiviral drug therapy. The HIV-1 DNA load in CD4 cells and CD4 percentage were found to be stable over the 48-week period. Delayed-type hypersensitivity to HIV-1 antigens increased after two inoculations with the HIV-1 Immunogen. In these two trials, no serious treatment-related adverse events were documented in the subjects. The two studies presented herein are the first to suggest that an immune-based therapy such as the HIV-1 Immunogen can be combined safely with antiviral drugs, supporting further study to evaluate the clinical utility of this approach.     

Autoimmunity related to IgM monoclonal gammopathy of undetermined significance. Peripheral neuropathy and connective tissue sensibilization caused by IgM M-proteins

In eight of 10 consecutive cases of IgM monoclonal gammopathy of undetermined significance (MGUS), the M-protein had specificity towards various tissues as estimated by direct and indirect immunofluorescence studies of skin and/or sural nerve biopsies. Five of the cases had neuropathy. In three of them, including two siblings with a demyelinating peripheral neuropathy, the IgM was bound to the myelin-associated glycoprotein (MAG) of peripheral nerves. One had axonal neuropathy with IgM activity against the peri- and endoneurium, while another case with post-infectious neuritis had IgM activity against structures in the endoneurium but no IgM autoimmunity in the direct fluorescence test. The latter improved clinically in parallel with a decrease in the M-protein indicating a pathogenetic role of the autoantibody. In three other cases, the IgM was bound to connective tissue structures, two of them also had plasma antibodies against the peri- and endoneurium in the indirect fluorescence test. Finally, two cases showed no reaction of the M-protein against any tissue structures. Since an autoimmune pathogenesis is suspected, the HLA types of seven patients are reported.     

Primary lymphadenopathic Kaposi's sarcoma in an immunocompetent 23-year-old man

An aggressive visceral form of Kaposi's sarcoma (KS) has been reported in immunosuppressed populations, most notably in patients with acquired immunodeficiency syndrome (AIDS). This presentation contrasts from the indolent skin lesions on the extremities of older males and is distinct enough in the young adult American population to have been included in the working definition of AIDS. The authors describe a case of primary lymphadenopathic KS in an immunocompetent heterosexual 23-year-old man with no epidemiologic, immunologic, or serologic evidence of AIDS. This report emphasizes that a diagnosis of KS in a young American male is not synonymous with the diagnosis of AIDS.     

Diagnostic difficulties in the interpretation of needle aspiration material from large renal cysts

In recent years, fine-needle-aspiration biopsies (FNA) have been widely used in the evaluation of renal masses, with false-positive FNA data being very uncommon. We present a case report of a 76-yr-old man with a 16-cm renal cyst and what was interpreted as an isolated calcified mural nodule. Following drainage of the main cyst fluid, FNA biopsy showed atypical cell clusters thought to be positive for malignancy. Subsequent surgery failed to disclose either a residual mural nodule or evidence of malignancy. Immunoperoxidase studies performed on both the cell block and actual cyst wall suggested that the abnormal cells were histiocytes. The diagnostic pitfalls of this case, along with a review of pertinent literature, are discussed. Diagn Cytopathol 1994; 11:380–384. © 1994 Wiley-Liss, Inc.     

Age-related changes of exercise-induced plasma catecholamines and neuropeptide Y responses in normal human subjects.

Age-related plasma noradrenaline and neuropeptide Y were evaluated in seven young (mean +/- SD, 28 +/- 3 years) and seven elderly (64 +/- 8 years) normal subjects during rest and different work loads on a cycle ergometer. In the supine and the sitting position plasma noradrenaline and neuropeptide Y were almost identical in the two groups. Plasma neuropeptide Y did not increase during exercise at 100 W for 15 min. At this load plasma noradrenaline levels were higher in the older subjects (mean +/- SEM, 0.97 +/- 0.12 vs. 0.60 +/- 0.09 ng ml-1). There was a significant correlation between plasma noradrenaline and the relative work load at 100 W (r = 0.794, P = 0.0007). At 75% of maximal work load plasma noradrenaline and neuropeptide Y were higher in the young group (1.84 +/- 0.16 vs. 1.26 +/- 0.13 ng ml-1 (noradrenaline) and 38 +/- 4 vs. 22 +/- 5 pmol l-1 (neuropeptide Y)). In the elderly group plasma neuropeptide Y did not increase during exercise and showed a tendency to fall below basal level 5 min post-exercise. It is concluded, that plasma noradrenaline does not increase more in older subjects during exercise when correcting for the generally lower physical fitness in this group compared to younger subjects, and that plasma neuropeptide Y does not increase during exercise in older subjects, suggesting an age-reduced capacity in this system.     

Effect of omeprazole and cimetidine on duodenal ulcer. A double-blind comparative trial

We conducted a double-blind randomized study of 132 patients to determine whether the new, investigational proton-pump inhibitor, omeprazole (30 mg per day), would accelerate healing and pain relief, as compared with cimetidine (1 g per day), in patients with duodenal ulcer. After two weeks of treatment, which was completed by all patients, the healing rates were 73 per cent in the omeprazole group and 46 per cent in the cimetidine group (P less than 0.01). After four weeks of treatment, which was completed by 118 patients, the corresponding figures were 92 and 74 per cent (P less than 0.05). In the omeprazole group 55 per cent of the patients were free of pain after the first week, as compared with 40 per cent of those treated with cimetidine (P greater than 0.05). No major clinical or biochemical side effects of omeprazole or cimetidine were noted. A six-month follow-up study revealed no significant difference between the recurrence rates after omeprazole and after cimetidine treatment. In May 1984 clinical trials with omeprazole were temporarily suspended, since a study of long-term toxicity in rats had shown the development of gastric carcinoid tumors.