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Eighteen patients with cryptococcal infection of the central nervous system seen during a 10-year period were reviewed. Eleven patients (61 per cent) were immunocompromised due to underlying disease and seven of these were on steroids, cyclophosphamide or both. Two-thirds of patients presented with the triad of fever, headache and neck rigidity suggesting meningitis; seizures and mental confusion were uncommon. A high index of suspicion was essential for diagnosis particularly in immunocompromised subjects, and the diagnosis was established by positive Indian-ink preparation, culture or raised antigen titre in the cerebrospinal fluid. CT scan was helpful for diagnosis and progress monitoring. Amphotericin B and 5-fluorocytosine were the mainstay of treatment, and imidazole derivatives and garlic may be helpful adjuncts. Mortality was 39 per cent, but full recovery was the usual outcome in those who survived. The prognosis was worse with immunocompromised patients, and of those who died, comma and/or convulsion on admission and marked cerebral oedema and hydrocephalus on CT were notable features.

Serum beta 2-microglobulin (beta 2-M) was measured in 115 patients with systemic lupus erythematosus (SLE) on 192 occasions. Raised beta 2-M was found in 16.4% of patients with only extrarenal manifestations of SLE, in 29.2% of patients with renal manifestation but an endogenous creatinine clearance greater than 80 ml/min/1.73 m2 and in 65.7% of patients with decreased creatinine clearance. beta 2-M was higher in SLE than non-SLE glomerulonephritides matched for creatinine clearance. Using an arbitrary scoring system, renal, extrarenal and serological activity correlated with beta 2-M. Changes in clinical activity on repeat studies were reflected by changes in beta 2-M. Serum beta 2-M can serve as a monitor of disease activity in SLE.

New techniques are are continuously being developed to obtain animal brain tissue that is as close as possible to its in vivo status. The brain-blowing technique provides a swift freezing of brain tissue (within 1 s) in which postmortem changes have been said to be minimal. Higher concentrations of glucose were present in brain samples removed by this method than have previously been found when the brain was frozen in situ, but at the same time the plasma levels of glucose were higher. It is suggested that, although the procedure did not appear to involve any stress, the hyperglycemia was stress related. Modifications of the procedure are described, by which these changes in blood glucose have been minimized.

Immunologically pure human transferrin type C (TfC) was isolated from the plasmas of 11 individual healthy donors. After conversion into the 2Fe-form, the preparations were analysed by polyacrylamide gel electrophoresis and chromatography on DEAE-cellulose. In all samples studied by either method the presence of three components, designated A, B and C, was observed. Calculations from eight chromatograms yielded the following relative proportions for the components: A:6%, B:62% and C:32%. The quantity of iron bound played no role in this chromatographic resolution. The components were immunologically identical but their sialic acid content increased inthe order of A less than B less than C. The presence of galactose as an ultimate residue of the oligosaccharide chains in TfC component A was confirmed by a biological test. This observation together with the results of earlier analyses for hexose, hexosamine and galactose in the subfractions from Behringwerke human transferrin, suggests that sialic acid is probably the only variable among TfC components A, B and C. Loss of sialic acid from component C during the isolation of TfC was excluded as an explanation for the presence of the other two components. The electrophoretic appearance of TfC samples from five patients with liver disease (chronic active hepatitis, cirrhosis or alcoholic liver) did not noticeably differ from that of TfC FROM HEALTHY PERSONS. Baboon transferrin resembles TfC with respect to sialic acid heterogeneity. This species was therefore studied to decide whether sialic acid is gradually lost from transferrin in the circulation or whether transferrin is not fully sialylated before discharge from the hepatocyte. Using DEAE-cellulose chromatography no difference was found between baboon transferrin molecules which were less than 6h old and those which had a mean age of 8.9 days. By inference it is suggested that the reason for the multiplicity of TfC is also likely to be biosynthetic.

Changes in the 300 MHz proton NMR spectrum of yeast tRNA-Phe induced by the removal of the Y-base from the anticodon loop are reversed when the dye proflavine is incorporated in its place. These observations correlate with our earlier interpretation of the NMR data that removal of the Y-base causes a change in the conformation of the anticodon stem. Such changes in stem conformation may in part be responsible for the differences in the biochemical properties of tRNA-Phe, tRNA-PhePF and tRNA-Phe-Y.

Thirty-one Chinese patients with peripheral T cell lymphoma (PTCL) were reviewed. Using the modified Japanese Lymphoma Group classification, there were nine (29%) of the pleomorphic type, 16 (52%) immunoblastic lymphadenopathy (IBL)-like, two (7%) T-zone lymphoma, and one (3%) Lennert's lymphoepithelioid type. Three (9%) were not classifiable. All were positive for T11 (E rosette receptor antigen). Fifty-four percent (15 of 28) were positive predominantly for T4 (helper T cell) and 46% (13/28) for T8 (suppressor T cell). The median age of the patients was 57 years. They usually presented with advanced disease, and while extranodal involvement was common, CNS disease was not seen. The IBL-like type was associated with a positive Coombs' test and polyclonal hypergammaglobulinemia. Five of the nine pleomorphic type were checked for antibody to HTLV-I virus and all were negative. PTCL was associated with poor prognosis, which was not influenced by the histologic subtypes and the T4/T8 phenotypes. The complete response rate of 13 consecutive patients who received the BACOP (bleomycin, doxorubicin, cyclophosphamide, vincristine, and prednisone) L17M regimen was significantly better than the 16 historic controls who received other less-intensive regiments, 84% v 19% (P less than .01). The relapse rate was also significantly lower, 9% v 100% (P less than .001). There appeared to be an improvement in the disease-free survival (DFS) (80% v 0% at 18 months), as well as the overall survival (60% v 36% at 18 months), but the differences did not reach statistical significance due to small sample sizes.

A 60-year-old man with a history of ingesting herbal medication and a 59-year-old woman with malignant lymphoma presented with painless jaundice and palpably enlarged gall-bladders. Abdominal ultrasonography confirmed that the gall-bladders were enlarged, but showed normal-sized biliary trees with no stones. The final diagnoses for these patients were drug-induced hepatitis with intrahepatic cholestasis and lymphomatous infiltration of the liver, respectively. A palpable gall bladder in cholestatic jaundice may not always be caused by extrahepatic biliary obstruction, and ultrasonography is very useful in ruling this out.

The intravitreous injection of an endotoxin of Escherichia coli 055:B5 (LPS; 0.1-0.5 microgram/50 microliters of saline) induces ocular inflammation in rabbits that is maximal 20-24 hours later and disappears by 4 days. The inflammation is characterized by an alteration in ocular vascular permeability (OVP) measured by the ocular extravasation of 125I-albumin and an outpouring of leukocytes, most of which are polymorphonuclear leukocytes (PMNs), as determined by histopathologic study. Nitrogen mustard (mechlorethamine, 1.75 mg/kg) administered 3 days prior to LPS virtually eliminates PMNs in the circulation and those infiltrating ocular tissues 20 hours after intravitreous LPS, and yet the average increase in vascular permeability is not different from that of controls. Cobra venom factor (CVF; 300-400 units) 7 hours before intravitreous LPS produces a greater than 90% decrease in both hemolytic complement activity and zymosan-inducible serum chemotactic activity; yet 20 hours after LPS, the OVP is the same in CVF-treated rabbits and controls. For comparison, an ocular passive Arthus reaction (ovalbumin-anti-ovalbumin) was significantly affected by CVF pretreatment. Chemotactic activity in the aqueous humor is found in both CVF-treated and control rabbits 20 hours after intravitreous LPS. This activity attracts rabbit, but not human, PMNs, is partially heat-sensitive, and is not inhibited when PMNs are preincubated with C5a. These results indicate that neither PMNs nor circulating complement determine the OVP following intravitreous LPS, and that the chemotactic activity present in aqueous humor at the height of the inflammatory response is not primarily C5a.

The clinical course of a woman with systemic lupus erythematosus demonstrated that renal involvement in this disease can change, both in the predominant site of renal injury and in the pattern of glomerular lesions. Over 50 months she had first tubulo-interstitial lupus nephritis with no glomerular change, then a membranous nephropathy with disappearance of tubulo-interstitial inflammation, and finally crescentic glomerulonephritis. This case emphasizes the need for close follow-up of all lupus patients regardless of their initial renal manifestations and pathology.

Male, English smooth haired guinea pigs were exposed to thermal decomposition products, i.e., smoke, generated by heating Douglas fir in an open system. Various amounts of Douglas fir were placed in a furnace, at room temperature, and heated at a rate of 11 degrees C/min until completely decomposed. Major decomposition occurred between 160 and 490 degrees C, and the animals were exposed during this time for a period of 30 min. Immediately before exposure and at various times after exposure, each animal was evaluated by whole-body plethysmography to measure tidal volume and respiratory frequency during air breathing as well as during challenge with 10% CO2. Exposure to smoke from Douglas fir resulted in a diminished ventilatory response to 10% CO2. Comparing the effect of wood smoke to the effect of smoke from polyvinylchloride from previous experiments wood smoke was found to be 10 times less potent than smoke from polyvinylchloride and animals recovered much more rapidly than with smoke from polyvinylchloride.

Study of the vascular endothelium has been greatly facilitated by the development of specific cell culture systems isolated from various tissues. We report herein a simple method for establishing a propagating cell culture system of microvascular endothelial cells derived from rat adipose tissue. In addition to the characteristic cobblestone appearance on light microscopy, the microvascular endothelial cells in culture also demonstrated the presence of other markers for large vessel endothelia. Electron microscopy revealed endothelium-specific Weibel-Palade bodies and abundant pinocytotic vesicles. Both retroperitoneal and epididymal endothelia demonstrated the presence of factor VIII antigen by immunofluorescent staining and prostacyclin production. Although there was no appreciable morphological difference between cultured retroperitoneal and epididymal microvascular endothelia, the replication rate of the former was significantly higher than that of the latter (P less than .05). Excessive replication of endothelial cells may play a role in the regional differences of adipose tissue mass in an organism.

Five subfractions were isolated on DEAE-cellulose from samples of a commercially available human transferrin preparation and their carbohydrate composition was analysed. Hexosamine, galactose and total hexose were determined in four subfractions and sialic acid in all five. The data obtained indicate that the excess number of electrophoretic bands observed in transferrin from this source is due to the loss of carbohydrates which only affects sialic acid and none of the other sugar types. The availability of the penultimate galactose residues as the terminal residues in the subfractions deficient in sialic acid was also confirmed by a biological test utilizing the rat liver. The reason for the gradual loss of sialic acid from transferrin is unknown. Freezing-thawing and lyophilization did not detectably affect the sialic acid content of purified transferrin. However, free sialic acid did appear in some preparations on storage. It is concluded that similar changes in the carbohydrate composition of other plasma glycoproteins before, during, or after purification can be expected to exert an adverse effect on their usefulness as metabolic tracers.

Pulmonary effects of inhalation exposures to hydrogen chloride were evaluated during and following exposure in male guinea pigs. During exposure, the respiratory rate and the time of onset of sensory or pulmonary irritation as evidenced by the change in respiratory pattern were measured. HCl inhalation resulted in both sensory and pulmonary irritation. The onset of sensory irritation took 6 min during HCl exposures at 320 ppm but less than 1 min at 680, 1040, and 1380 ppm. The onset of pulmonary irritation showed a concentration-response relationship, the higher the concentration the earlier the onset. Following exposure to HCl, animals were evaluated using a pulmonary performance test based on their ventilatory response (respiratory rate and tidal volume) during challenge with 10% CO2. The maximal respiratory frequency achieved during the CO2 challenge was lower in the HCl-exposed animals than in the controls in a HCl concentration-dependent fashion, but HCl had no apparent effect on the maximal tidal volume achieved during CO2 challenges. HCl exposure also affected baseline respiratory rate and tidal volume of the animals after exposure. Impairments of the respiratory function were also supported by evidence of morphological injury in both the airways and the alveolar region.

Activation of protein kinase C (PKC) facilitates long-term potentiation (LTP), a model of memory, and increases its substrate protein F1 (aka GAP43) phosphorylation in direct relation to synaptic enhancement. Unsaturated fatty acids (c-FAs) which activate purified PKC, when injected into hippocampus, enhance LTP. To determine if dietary c-FAs could alter memory itself as well as brain PKC substrate (F1) metabolism, rats were maintained for 10 weeks on fatty acid diets enriched in mono-unsaturated oleic acid (OA; 20% olive oil, w/w), or a mono- and di-unsaturated mixture of oleate/linoleate (O/L; 20% corn oil), or a saturated fatty acid diet of laurate/myristate (L/M; 20% hydrogenated coconut oil). The O/L diet group was superior to the OA and L/M groups in spatial memory performance after the first two weeks of acquisition and in later achievement of criterion performance. The O/L diet had a significantly higher hippocampal protein F1 in vitro phosphorylation than in both the OA and L/M in trained and non-trained animals. Significantly, animals that made fewer errors showed higher F1 phosphorylation (r = -0.70). Diet both increases brain PKC substrate phosphorylation and enhances maze learning, confirming the feasibility of enhancing learning and memory by dietary regimens derived from basic neurochemical studies of synaptic plasticity.

We report a 37 year old Chinese woman with systemic lupus erythematosus complicated by concomitant cytomegalovirus pneumonia and alveolar haemorrhage. The cytomegalovirus pneumonia may have been causally related to the alveolar haemorrhage.

The distribution of HLA-A, B, and DR alleles has been studied in 100 Chinese patients with systemic lupus erythematosus and in 100 healthy Chinese controls. Complement components factor B, C4A and C4B were studied in 72 patients and 61 controls. There was no significant difference between patients and controls in the distribution of HLA-A, HLA-B, factor B and C4B alleles, but there was a significant excess of HLA-DR2 and C4A null in the patients. An unusual variant of C4B was found in 6 patients and 1 control. The possible role of haplotypes is considered in interpreting these results and relating them to previous findings in Chinese.

Zygomycosis often occurs in patients with an underlying disease, e.g., diabetes mellitus, leukemia, and lymphoma, or an immunocompromised state. This report discusses a case of a 21-year-old woman with systemic lupus erythematosus complicated by uremia, acidosis, steroid therapy, prolonged antimicrobial therapy, and disseminated zygomycosis.

Newborn rats have about a 20-fold higher concentration of metallothionein in the liver than does the adult rat. This marked increase in hepatic metallothionein does not result in a lower acute toxicity to cadmium in newborn rats; it does not markedly increase the distribution of cadmium to the liver, decrease its concentration in other tissues, or produce a slower removal of the cadmium from younger animals. The toxicity of cadmium in the newborn rat appears to be more dependent on other factors such as the development of the blood-brain barrier and the stage of development of the testes than on the amount of metallothionein in the liver. The results of this study suggest that we should probably reevaluate the role of metallothionein in producing tolerance to cadmium.

The distribution of urotensin I (UI) and corticotropin-releasing factor (CRF) immunoreactive (IR) structures was studied in the central nervous system (CNS) of the white sucker using the peroxidase-antiperoxidase immunocytochemical procedure. The close sequence homology between both peptides resulted in a high degree of crossreactivity. This was resolved by saturating the antisera solutions with heterologous antigens and specificity tests were done by adding excess of homologous peptides. UI immunoreactivity was seen in all of the identifiable caudal spinal cord neurosecretory cells, in their processes projecting to the urophysis, in thin beaded fibres coursing along the spinal cord, in brain stem, hypothalamus, proximal pars distalis and, especially, in the telencephalon. Some IR-UI specific and IR-CRF specific parvocellular neurons were also identified in the caudo-ventral tuberal region and ventral telencephalon. The IR-CRF was mainly present in parvocellular and magnocellular perikarya of the nucleus preopticus and in the preoptic-neurohypophysial pathway. Dense networks of IR-CRF reacting beaded fibres were also located in the lateral and posterior recessus nuclei. In the pituitary, IR-CRF fibre bundles were seen mainly in the neurointermediate lobe and in the rostral pars distalis. The cells of origin of the extraurophyseal system of IR-UI fibres in the sucker CNS have not been identified. The distribution of CRF immunostaining correlates well with the documented knowledge of CNS structures involved in the control of ACTH secretion in the goldfish. The probability of the occurrence of two UI-CRF related molecules, or of two different forms resulting from a common precursor molecule, forming two separate neuronal systems in the sucker CNS seems likely.

Pyridoxal 5'-phosphate (PLP) concentrations were measured in brains of rats to determine whether a deficiency of this coenzyme was a common feature in hepatic coma, ethanol intoxication, and in animals treated with L-dopa or with 5-hydroxytryptophan (5-HTP) alone or with inhibitors of MAO or of L-aromatic amino acid decarboxylase. These treatments have been shown previously to be associated with reduced conversion of glucose to amino acids in brain. Cerebral PLP concentrations were reduced after some of these treatments, notably injection of ethanol, or L-dopa alone or with beta-phenylisopropylhydrazine, an inhibitor of MAO, or of 5-HTP together with N-[beta-(chlorophenoxy)ethyl]cyclopropylamine hydrochloride, Lilly 51641, another MAO inhibitor. However, in other circumstances where inhibition of conversion of glucose to amino acids has been shown (treatment with 5-HTP, or with Lilly 51641 or with [N-(D,L-seryl)-N'-2,3,4-trihydroxybenzyl]hydrazine, an inhibitor of L-aromatic amino acid decarboxylase, together with L-dopa or with 5-HTP), PLP levels in brain were unchanged, or were increased (in hepatectomized rats).

Resonances in the low-field (11-15 ppm) nuclear magnetic resonance spectrum (NMR) of tRNA molecules arise from secondary and tertiary structure base pairs (1 resonance for each base pair) as well as tertiary structure hydrogen bonds. An accurate method for integrating the low-field spectra has been developed and applied to seven different tRNA. In the presence of high levels of magnesium (10 mM free magnesium) the number of resonances (base pairs) per molecule is typically 3-4 more than the number predicted by the cloverleaf model. These results confirm our recent proposal that, under proper conditions, most tRNA exhibit 3-4 tertiary structure interactions in solution, which are also observed in x-ray diffraction studies of yeast tRNAPhe. In addition to common resonances in the 11-15 ppm region, there are common resonances at 10.5 and 9.5 ppm. A critique of methods used to integrate the low-field spectra is given and possible sources of error are indicated. The discrepancy between our present results and previous studies, which indicated that the number of base pairs per molecule was close to the number predicted by the cloverleaf model, can be attributed partly to differences in magnesium concentration and partly to inaccuracies inherent in the integration methods used.

Two manual laborers were exposed to dimethyl sulfate during work and sustained mucosal injury to the eyes and respiratory tract. In one of them, noncardiogenic pulmonary edema occurred and improved with high-dose methylprednisolone. On follow-up for 10 months, this patient developed persistent productive cough with no evidence of bronchiectasis or bronchial hyperreactivity.

Serum creatinine and beta 2-microglobulin levels, endogenous creatinine clearance, the urinary beta 2-microglobulin excretion rate, and urinary protein levels were monitored serially in 29 patients with duodenal ulcers randomly allocated to receive eight weeks of treatment with cimetidine, ranitidine, or an antacid. A clinically insignificant increase in endogenous creatinine clearance was noted in patients given ranitidine. No adverse change in any of the variables measured was detected in any group of patients during the 12-week period of study.

The effect of removing the Y base from the anticodon loop of yeast tRNA(Phe) has been examined by high-resolution proton nuclear magnetic resonance spectroscopy and optical melting. Analysis of the changes in the nuclear magnetic resonance spectra indicate that the removal of the Y base produces a small conformational change in the anticodon stem in which all the interbase separations are increased by approximately 0.2 A. The temperature dependence of the nuclear magnetic resonance spectra and the optical melting measurements indicate that the high temperature stability of tRNA(Phe) is decreased by removal of the Y base. With the exception of the anticodon stem, the secondary structure of the other helical stems of the molecule appear to be unaltered when the Y base is excised.

High-resolution 300-MHz proton nuclear magnetic resonance spectra of the hydrogen-bounded protons in three different purified tRNA molecules are presented. The resonances in the region between -11 and -15 ppm from 2,2-dimethyl-2-silapentane-5-sulfonate (DSS) are assigned to the ring NH protons of specific base pairs by two approaches. First, intrinsic positions of -14.8 ppm and -13.7 ppm are taken for the AU and GC ring NH protons, respectively, and the spectra are calculated by including ring current shifts from the nearest neighbors. The spectra calculated in this way on the basis of the cloverleaf are in good agreement with the observed. Second, fragments of yeast tRNA(Phe) were obtained, which helped in assignments of the spectrum of intact molecules. The close agreement strongly supports the cloverleaf model. Tertiary structural features were determined in a few cases where the ring currents at the terminal base pairs of helical regions depended upon stacking of the helices. In this way, we were able to show that in Escherichia coli tRNA(Glu) the CCA stem forms a continuous helix with the TPsiC stem, which is in accord with the preliminary x-ray structure of yeast tRNA(Phe), suggesting that this stacking is observed in solution and may be a general property of different tRNA molecules. Similar reasoning suggests that in E. coli tRNA(fMet) G-27 is stacked upon the dihydrouridine helix.