Origin and differentiation of natural killer cells. III. Relationship between the precursors and effectors of natural killer and natural cytotoxic activity.
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Biomedical subjects
Publications and source records attributed to V Kumar.
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We report here direct immunofluorescence studies of normal skin biopsies that exhibited only complement C3 staining in intercellular areas of epithelium with a view toward evaluating the significance of such findings. During a 5-year period, 11,000 skin biopsy specimens were examined for in vivo binding of immunoglobulins, fibrin, and complement C3 by means of defined direct immunofluorescence methods. Four of ten patients demonstrating intercellular C3 deposits alone had drug-related reactions or erythema multiforme, and four were subsequently shown to have a connective tissue disease. Pemphigus was ruled out in all ten cases in these retrospective studies. These observations indicate that the finding of intercellular C3 deposits in the absence of IgG in normal skin is not a sign of pemphigus but, rather, a sign either of an unusual type of drug reaction or, possibly, of some connective tissue disease. However, the finding of intercellular C3 plus IgG (with or without other immunoglobulins) is a sign of pemphigus. The mechanism of C3 deposition without immunoglobulins is not clear.
The specificity and sensitivity of the recently reported IgA-class antiendomysial antibody test for gluten-sensitive enteropathy were evaluated in four double-blind studies involving the sera of fifty-seven patients with dermatitis herpetiformis who were not on a gluten-free diet and ninety-seven assorted control sera. The control sera provided by the four centers included the sera of nineteen patients with dermatitis herpetiformis and two with celiac disease who were on a gluten-free diet, the sera of five normal subjects with human lymphocyte antigens (B8 locus), the sera of thirteen patients with linear IgA bullous dermatosis, and fifty-eight other control sera, mostly from patients with other bullous diseases and other dermatoses. The frequency of IgA antiendomysial antibody in these coded studies was zero of ninety-seven control sera and thirty-four of fifty-seven sera (60%) from patients with dermatitis herpetiformis who were not on a gluten-free diet. The pathogenic role of IgA antiendomysial antibodies in dermatitis herpetiformis and celiac disease is suggested not only by their high degree of disease sensitivity and specificity but also by their formation in response to gluten challenge, their appearance before gut changes, and the in vitro binding of gliadin to the antiendomysial antibody antigen sites. These and other findings in this study and in the literature suggest that gluten-sensitive enteropathy is immunologically mediated and that IgA antiendomysial antibodies play a significant pathogenetic role.
Aminoglycoside antibiotics including kanamycin A, tobramycin, and the gentamicin C complex reacted with 1 mol of disodium carbenicillin to give products derived from acylation of their amino groups by the beta-lactam function of the carbenicillin. Amikacin was acylated by two carbenicillin units. Chromatographic analysis of fragments from the acid hydrolysis of these derivatives showed that the preferred site of acylation was in the 2-deoxystreptamine unit of the aminoglycosides. The two sites of acylation in amikacin were the 6'-amino group and the amino group in the aminohydroxybutyryl substituent. The derivatives had almost no antibacterial activity, and they were not toxic.
We have utilized a mouse mutant (C.B-17 scid) that lacks functional T and B lymphocytes to examine the relationship among transplantable progenitors of natural killer (NK) cells, T cells, and B cells. The NK-progenitor cells contained in the bone marrow were detected by their ability to generate mature NK cells, following transfer of bone marrow cells into NK cell-depleted and lethally irradiated mice. Regeneration of NK activity in the recipient mice was monitored by two different assays: the ability to rapidly clear infused YAC-1 cells in vivo and the ability of spleen cells to lyse YAC-1 cells in vitro. Recipients were also tested for the presence of mitogen-responsive T and B cells and for prethymocytes (thymus-repopulating cells). We found that the capacity of C.B-17 scid bone marrow cells to generate mature NK cells was equivalent to that of control C.B-17 bone marrow cells. The regenerated NK cells shared similar functional activity and surface phenotype. In contrast, bone marrow cells from C.B-17 scid mice failed to generate thymocytes and peripheral T and B cells. These data indicate that the transplantable NK-progenitor cells are not defective or deficient in C.B-17 scid mice and, therefore, are distinct from the transplantable progenitor(s) of T and B cells.
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Administration of benzene-soluble fraction (FAE) and benzene-insoluble fraction (FAR) of fly ash for 3 consecutive days to rats significantly raised cytochrome P-450 levels, aryl hydrocarbon hydroxylase (AHH) activity, and glutathione S-transferase activity in liver. This treatment also significantly increased pulmonary AHH and glutathione S-transferase activity. Intratracheal administration of FAR (5 mg/100 g body weight) alone for 6 consecutive days also significantly increased hepatic cytochrome P-450 levels and the activity of glutathione S-transferase. Intragastric administration of retinyl palmitate (5000 IU/100 g body weight), along with intratracheal FAE and FAR administration, significantly reduced P-450 levels, activity of glutathione S-transferase in liver, and activity of AHH and glutathione S-transferase in lung of rats. Intraperitoneal administration of citrate (40 mg/100 g body weight) along with FAR significantly reduced FAR-induced increase in hepatic cytochrome P-450 levels and glutathione S-transferase activity. The activity of AHH was not affected by these treatments.
Polycyclic aromatic hydrocarbons (PAH) were extracted from coal fly ash collected from the electrostatic precipitator of a thermal power plant. The PAH extract was given intratracheally daily to pregnant rats (2 mg/100 g body weight) on d 18 and 19 of gestation. In addition on d 19 of gestation rats were also given [3H]benzo[a]pyrene intratracheally. Rats were sacrificed on d 20 of gestation, and the distribution of [3H]benzo[a]pyrene radioactivity and PAH of coal fly ash was studied in maternal lung, liver, and placenta, as well as in the liver and lung of the fetus. The radioactivity of intratracheally given benzo[a]pyrene was found in liver (68%), placenta (4%), fetal lung (1.9%), and fetal liver (1.4%) of maternal lung. Intratracheally administered PAH of coal fly ash were translocated to maternal liver and placenta, as well as to the liver and lung of the fetus. PAH of coal fly ash were also metabolized to several minor and major metabolites by maternal lung, liver, and placenta, as well as by the maternal fetal liver and lung. Some of the PAH metabolites in lung and liver were common; however, the major metabolite of liver, M-16, was different from the major metabolite M-16 of lung. The major PAH metabolite of placenta, M-5, and fetal liver, F-12, were common PAH metabolites. M-2 and M-6 of the placenta and F-5 and F-10 of the fetal lung were also common.
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Sequential thermodilution measurements of cardiac output in mechanically ventilated patients undergoing cardiac surgery demonstrated a cyclic modulation which correlated with changes in airway pressure, and was not affected by opening the pericardium. There was no satisfactory point for single measurements, which suggests that random thermodilution measurements of cardiac output during intermittent positive-pressure ventilation should be avoided, even when triplicate measurements are performed. To estimate the mean cardiac output, at least two measurements should be made at predetermined points of the ventilatory cycle. We recommend paired measurements at midinspiration and end-expiration.
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Scl 70 antibodies were tested for in 107 patients with systemic sclerosis: 68 with acrosclerosis and 39 with diffuse scleroderma. Anticentromere antibodies (ACA) and other antinuclear antibodies (ANA) were tested for by indirect immunofluorescence on HEp-2 cells. Positive results for Scl 70 antibodies were obtained in 77% of cases of diffuse scleroderma and 44% of acrosclerosis. ACA and Scl 70 antibodies were found to be mutually exclusive. If acrosclerosis cases positive for anticentromere antibodies are excluded, the percentage of acrosclerosis cases positive for Scl 70 was 63%. ACA were found to be a marker of a benign, abortive subset of acrosclerosis with almost no cutaneous involvement (CREST), whereas Scl 70 did not discriminate between acrosclerosis and diffuse scleroderma. On HEp-2 cells Scl 70 positive sera gave a characteristic, fine speckled, almost homogeneous nuclear staining pattern.
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Procyclidine was administered to 25 chronic psychotic inpatients, stabilised on chlorpromazine, haloperidol or fluphenazine decanoate injection. We observed a significant reduction in mean serum levels of all three neuroleptic drugs which was reversed on stopping procyclidine and was inversely correlated with mean serum procyclidine levels. No significant alterations occurred on the BPRS scores or in serum prolactin levels throughout the study in any of the three groups. Possible mechanisms of this interaction and its clinical relevance are discussed.
Cicatricial pemphigoid is a chronic subepidermal bullous dermatosis which primarily involves the mucous membranes. It is a disease found almost exclusively middle-aged and elderly persons. This report describes a case of cicatricial pemphigoid with onset at age 5 and involving primarily the mucous membranes of the mouth and eyes. The patient cleared well on 40 mg of Prednisone and has been maintained on a regimen of 7.5 mg of Prednisone every other day.
Groups of photosensitive, unstimulated or stimulated, male blackheaded buntings were subjected to photoregimes of 15 hr of green light of three intensities and 9 hr of dark per day. In some groups green light was interrupted with 90 min of bright fluorescent light at different times in the subjective day. While gonads did not develop or regressed in some groups, birds in others behaved as if exposed to long daylengths. The results besides suggesting the involvement of endogenous circadian rhythm during initiation and maintenance of gonadal growth indicate that the reproductive rhythms are entrained and induced by environmental photoperiod.
Mice were irradiated and infused with BALB/c Friend virus-induced FLD-3 erythroleukemia cells. Growth of the cells was estimated by measuring splenic incorporation of 5-iodo-2'-deoxyuridine-125I 5 days after cell transfer. BALB/cJ and C3H mice were 'poor responders' in that FLD-3 cells grew well in their spleens, while mice of other strains were 'good responders', resisting the growth of FLD-3 cells. No H-2 or Fv genetic locus was associated with resistance. Athymic nude mice and mice depleted of marrow tissue by 89Sr or estradiol resisted FLD-3 cells, indicating that the effectors were thymus- and marrow-independent. Silica, carrageenan and Propionibacterium acnes organisms all altered resistance, suggesting a function of macrophages. Neither interferon nor anti-interferon serum treatment altered resistance. Anti-asialo GM1 serum inhibited resistance to FLD-3 cells in vivo and inhibited natural cytotoxic (NC) activity against FLD-3 cells in vitro. NC (FLD-3) activity was greatly decreased in spleens 3 days after irradiation, in contrast with NK (YAC-1) and NC(WEHI-164.1) activities. Moreover, a 3-day delay in infusion of FLD-3 cells 'synergized' with silica in weakening genetic resistance in vivo. Thus, natural immunity to FLD-3 cells in vivo differs from that of genetic resistance to normal bone marrow cell allografts, and the lysis of FLD-3 cells in vitro seems to be mediated by cells which do not easily fit into the definition of natural killer (NK) or natural cytotoxic (NC) cells.